Relationship between pterygomaxillary fissure morphology and maxillary/mandibular position : A cone beam computed tomography assessment.

PURPOSE: The aim of this study was to investigate the possible correlation between maxillary and mandibular positioning via cephalometric analysis with pterygomaxillary fissure (PMF) morphology using cone beam computed tomography (CBCT). METHODS: In this study, CBCT images from 825 individuals (448 female, 377 male; age range was 18-91 years with this cohort) were analyzed; PMF length and width were measured. Three-dimensional cephalometric analysis was also performed using cephalometric analysis software. The landmarks and measurements in relation to maxillary and mandibular positions were identified and performed for the cephalometric analysis. Analysis of variance (ANOVA) was used for comparison of the parameters, while the Bonferroni test was used for multiple comparisons. Pearson's test was also used to assess the correlations between the parameters. RESULTS: The results showed that males had significantly larger PMF length (p < 0.001) and width (p < 0.001) compared to females. The mean PMF length was 17.7 mm (standard deviation [SD] 3.2 mm) for right and 17.7 mm (SD 3.3 mm) for left but were not significantly different (p > 0.05). In terms of the cephalometric measurements, a significant correlation was found between upper central incisor (U1toAperp2D) and posterior facial height (PostFaceHtSGo2D) and PMF length, while correlations were found between PMF width and several cephalometric parameters such as lower lip (LwLiptoEPln2D and LwLiptoHLine2D) and occlusal plane (OPtoFHAng2D) (p < 0.05). CONCLUSION: A significant relationship was observed between PMF morphology and the position of the maxilla or mandible. PMF lengths and widths were larger in males than females. Posteroanterior maxillary and mandibular lengths and posterior facial height are associated with PMF length and width.

Oncologic doses of zoledronic acid induce site specific suppression of bone modelling in rice rats.

OBJECTIVES: To examine the effect of zoledronic acid (ZOL) on cortical bone modelling and healing of extraction sockets in the jaw bones of a rodent model. We hypothesized ZOL suppresses both the bone formation in the modelling mode in the jaw bones and alters the extraction site healing. MATERIAL & METHODS: Rice rats were administered saline solution and two dose regimens of ZOL: 0.1 mg/kg, twice a week, for 4 weeks (n=17, saline=8 & ZOL=9) and a higher dose of 0.4 mg/kg, weekly, for 9 weeks (n=30, saline=15 & ZOL=15). Two pairs of fluorochrome bone labels were administered. Extraction of maxillary teeth was performed in maxilla. Mineral apposition rate, mineralizing surface and bone formation rate (BFR) were quantified on periodontal (PDL), alveolar and basal bone surfaces, and in the trabecular bone of proximal tibia. Bone volume (BV) was evaluated at extraction sockets. Multivariate Gaussian models were used to account for repeated measurements, and analyzes were conducted in SAS V9.3. RESULTS: ZOL suppressed bone modelling (BFR/BS) at the PDL surfaces in the mandible (P<.05), but its effect was not significant at the periosteal surfaces of both jaws. BV for the healing sockets of ZOL treated animals was not significantly different (P=.07) compared to the saline group. ZOL suppressive effect was higher in the tibia compared to the jaws. CONCLUSION: ZOL severely suppresses coupled remodelling in the tibia, and the suppression of bone formation in the modelling mode in the jaws demonstrates the site specific effects of ZOL in rice rats.

Case report: multiple keratocystic odontogenic tumour in a non-syndromal pediatric patient.

BACKGROUND: Keratocystic odontogenic tumour (KCOT) is an odontogenic tumour which stems from the odontogenic organs mostly localised in the lower jaw, particularly posterior body and ascending ramus of the mandible. The majority of these tumours are single lesions. When detected in the jaw in multiple forms, these cysts are seen in association with Gorlin Goltz/Basal cell naevus syndrome. However a few cases of non-syndromal multiple keratocystic odontogenic tumour have been reported in the literature. CASE REPORT: We report a case of multiple keratocystic odontogenic tumour in a 13-year-old girl demonstrated by panoramic radiography and cone beam computed tomography (CBCT). The differential diagnosis, treatment and imaging modalities are also discussed.

Comparison of linear and angular measurements using two-dimensional conventional methods and three-dimensional cone beam CT images reconstructed from a volumetric rendering program in vivo.

OBJECTIVE: The aim of this study was to compare the linear and angular measurements made on two-dimensional (2D) conventional cephalometric images and three-dimensional (3D) cone beam CT (CBCT) generated cephalograms derived from a 3D volumetric rendering program. METHODS: Pre-treatment cephalometric digital radiographs of 11 patients and their corresponding CBCT images were randomly selected. The digital cephalometric radiographs were traced using Vista Dent OC (GAC International, Inc Bohemia, NY) and by hand. CBCT and Maxilim® (Medicim, Sint-Niklass, Belgium) software were used to generate cephalograms from the CBCT data set that were then linked to the 3D hard-tissue surface representations. In total, 16 cephalometric landmarks were identified and 18 widely used measurements (11 linear and 7 angular) were performed by 2 independent observers. Intraobserver reliability was assessed by calculating intraclass correlation coefficients (ICC), interobserver reliability was assessed with Student t-test and analysis of variance (ANOVA). Mann-Whitney U-tests and Kruskal-Wallis H tests were also used to compare the three methods (P < 0.05). RESULTS: The results demonstrated no statistically significant difference between interobserver analyses for CBCT-generated cephalograms (P < 0.05), except for Gonion-Menton (Go-Me) and Condylion-Gnathion (Co-Gn). Intraobserver examinations showed low ICCs, which was an indication of poor reproducibility for Go-Me and Sella-Nasion (S-N) in CBCT-generated cephalograms and poor reproducibility for Articulare-Gonion (Ar-Go) in the 2D hand tracing method (P < 0.05). No statistical significance was found for Vista Dent OC measurements (P > 0.05). CONCLUSIONS: Measurements from in vivo CBCT-generated cephalograms from Maxilim® software were found to be similar to conventional images. Thus, owing to higher radiation exposure, CBCT examinations should only be used when the inherent 3D information could improve the outcome of treatment.

Investigation of pneumatized articular eminence in orthodontic malocclusions.

OBJECTIVES: To investigate the prevalence and characteristics of pneumatized articular tubercule (PAT) or eminence in an orthodontic patient population and to examine the possible correlations between different orthodontic malocclusions and pneumatized articular eminence types. SETTING AND SAMPLE POPULATION: Department of Orthodontics, Faculty of Dentistry, Ankara University, Turkey. MATERIAL AND METHODS: Pre-treatment panoramic radiographs were evaluated retrospectively from files of 1405 children and adolescents (459 boys and 946 girls) having various types of malocclusions. Diagnosis of PAT on the radiographs was recorded only if unequivocal pneumatization of the articular eminence could be seen or if the defect was located in the articular eminence posterior to the zygomaticotemporal suture, as a well-defined unilocular- or multilocular radiolucency. PAT was classified as unilocular or multilocular and unilateral or bilateral. Chi-square test was performed to evaluate age, gender, localization, type of malocclusion and prevalence differences. RESULTS: Sixty-six pneumatized articular eminences were found in 48 patients, representing a prevalence of 3.42%. The results of chi-square test showed no statistically significant differences considering age (p = 0.516), gender (p = 0.719), type of malocclusion (p = 0.155) and localization (p = 0.738). CONCLUSIONS: A relatively high rate of pneumatized articular eminence was observed among patients with orthodontic malocclusions (3.42%) when compared to the general population studies. Knowledge about these structures is helpful for the interpretation of cephalometric and panoramic radiographs and provides valuable information especially prior to temporomandibular joint surgery to avoid intra-operative reconstruction and complications.

Splenic artery Doppler in the prediction of the small-for-gestational age infant.

OBJECTIVES: We hypothesized that, as with other areas of the peripheral circulation, fetal splenic artery blood flow undergoes changes in small-for-gestational age (SGA) fetuses due to a redistribution of cardiac output, and that the Doppler peak systolic velocity (PSV) reflects such changes and thus may be used to predict fetuses being SGA. METHODS: Splenic artery Doppler PSV, end-diastolic velocity (EDV), resistance index (RI) and umbilical artery RI were measured prospectively in fetuses at risk for being SGA at birth. Normal reference data were generated from appropriately grown fetuses delivering at > or = 37 weeks without complications, and SGA was defined as birth weight < 10th percentile. The Doppler indices were expressed as multiples of the normal median (MoM) for gestational age. Using receiver operating characteristic curves, optimal Doppler thresholds for the detection of SGA cases were determined and the areas under the curves calculated. The analysis was limited to singleton pregnancies delivered within 2 weeks of the last Doppler examination. RESULTS: There were 88 study patients of which 60 had SGA babies. The mean gestational age at Doppler examination was 31.4 weeks with a mean interval of 5.6 days from Doppler to delivery. The splenic artery PSV was lower in SGA, compared to normal cases: mean PSV (MoM), 0.93 vs. 1.09, respectively (P = 0.0001). The sensitivity, specificity and area under the curve were 70.0%, 72% and 0.734, respectively (P < 0.003), for the PSV in the prediction of delivery of a SGA fetus. For the splenic artery RI, values were 70%, 46% and 0.539, respectively (not significantly different), and for umbilical artery RI these were 70%, 61% and 0.689, respectively (P < 0.01). Splenic artery EDV was significantly reduced in SGA vs. normally grown fetuses (0.924 MoM vs. 1.145 MoM, P = 0.007). CONCLUSIONS: Fetal splenic artery PSV decreases in SGA infants, and is a strong predictor of the delivery of a SGA infant. It appears to be superior to the standard Doppler index, the RI, in predicting this outcome.

Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization.

OBJECTIVE: Middle cerebral artery peak systolic velocity has been successfully used for timing the first cordocentesis in fetuses who are at risk for anemia because of maternal red cell alloimmunization. The effects on Doppler velocimetry after the intrauterine transfusion of adult blood to these fetuses are unknown. The objective of this study was to assess the applicability of Doppler methods for the prediction of severe anemia in fetuses who had undergone 1 previous intrauterine transfusion. STUDY DESIGN: Doppler examination of middle cerebral artery peak systolic velocity was performed before cordocentesis in 64 fetuses who had undergone 1 previous intrauterine transfusion. Timing of the second intrauterine transfusion was based on traditional criteria. Anemia was defined as mild (hemoglobin value between 0.84 and 0.65 multiples of the median), moderate (hemoglobin value <0.65-0.55 multiples of the median), and severe (hemoglobin value <0.55 multiples of the median). Receiver operator characteristic curves were created to select threshold values to identify the 3 degrees of anemia with a sensitivity of 100%. RESULTS: Gestational age at the Doppler study ranged from 19 to 36 weeks. Forty-six fetuses (72%) were not or mildly anemic; 7 fetuses (11%) were moderately anemic, and 11 fetuses (17%) were severely anemic. Middle cerebral artery peak systolic velocity for the prediction of severe, moderate, and mild anemia at a sensitivity of 100% showed false-positive rates of 6%, 37%, and 70%, respectively. CONCLUSION: In fetuses who have undergone 1 previous intrauterine transfusion because of maternal red cell alloimmunization, timing the second intrauterine transfusion can be determined noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Ratio of nuchal thickness to humerus length for Down syndrome detection.

OBJECTIVE: Ultrasonographic biometry markers are now being used clinically to adjust Down syndrome risk. The limitations are that the definitions of "abnormal" measurements used are arbitrary, thus reducing screening performance, and also that patient-specific Down syndrome risks cannot be calculated. We report a new ultrasonographic algorithm that is sensitive for Down syndrome detection and that estimates individual risk. STUDY DESIGN: Overall in fetal populations with Down syndrome the humerus length is decreased, whereas the nuchal thickness is increased relative to that of a normal population. The nuchal thickness/humerus length ratio therefore shows an even greater increase and magnifies the separation between Down syndrome and healthy groups. Prospective data were collected in midtrimester amniocentesis cases. A regression equation for the median nuchal thickness/humerus length ratio based on biparietal partial diameter was generated. The Down syndrome likelihood ratio, or the odds on the basis of the nuchal thickness/humerus length ratio (multiples of the median), was multiplied by the age-related risk to give the posterior Down syndrome risk. Charts for rapid estimation of individual Down syndrome risk on the basis of maternal age and the nuchal thickness/humerus length ratio were constructed. RESULTS: There were 94 cases of Down syndrome and 4700 cases in which the karyotype was normal. The mean (+/-SD) gestational age of the study population was 16.1 +/- 1.6 weeks. Thirty-three fetuses with Down syndrome and 68 karyotypically normal fetuses had gross anomalies. The equation for the expected median nuchal thickness/humerus length ratio was as follows: 10e(1.7163 - 0.0292) x BPD + 0.0003 x BPD2, where BPD is the biparietal diameter. In the overall study population the nuchal thickness/humerus length ratio and maternal age had a 79.8% detection rate at a 22.1% false-positive rate, compared with maternal age plus humerus length (sensitivity, 55.1%) or maternal age plus nuchal thickness (sensitivity, 66.7%) at the same false-positive rate. For women > or =35 years old the values were 80% and 22.0%, respectively. CONCLUSIONS: We report an ultrasonographic biometry algorithm that, in combination with maternal age, detects 79.6% of Down syndrome cases in a high-risk group. Individual Down syndrome risk can be quickly calculated at the bedside and made available to women who desire this information before making a decision on amniocentesis. On the basis of published standards, ultrasonographic biometry as described would be a cost-effective alternative to amniocentesis in this high-risk group.

Comparison of urinary hyperglycosylated human chorionic gonadotropin concentration with the serum triple screen for Down syndrome detection in high-risk pregnancies.

OBJECTIVE: Both modest screening performance and declining patient and physician acceptance have stimulated interest in alternative markers to the triple screen for the detection of Down syndrome. Our purpose was to compare the concentration of a single urinary analyte, hyperglycosylated human chorionic gonadotropin, with the serum triple screen (alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol concentrations combined with age) for second-trimester Down syndrome detection. STUDY DESIGN: Urine and blood were obtained from pregnant women in the second trimester undergoing genetic amniocentesis. Urinary hyperglycosylated human chorionic gonadotropin concentration and serum triple-screen values were measured. Individuals undergoing amniocentesis because of abnormal triple-screen results were excluded. Individual Down syndrome risks on the basis of urinary hyperglycosylated human chorionic gonadotropin concentration plus maternal age and on the basis of the triple-screen results were calculated. For each algorithm the sensitivity and false-positive rate for Down syndrome detection at different risk thresholds were determined. From these values receiver operating characteristic curves were constructed, and the area under the curve was determined for each algorithm. Finally, the performance of a new combination in which urinary hyperglycosylated human chorionic gonadotropin concentration replaced serum human chorionic gonadotropin concentration in the triple screen was ascertained. RESULTS: We studied 24 pregnancies complicated by Down syndrome and 500 unaffected pregnancies between 14 and 22 weeks' gestation in a mostly white (93.5%) population undergoing amniocentesis primarily because of advanced maternal age. The sensitivity and false-positive rate for urinary hyperglycosylated human chorionic gonadotropin concentration were 75. 0% and 5.6%, respectively, whereas those for the triple screen were 75.0% and 33.2%, respectively. Urinary hyperglycosylated human chorionic gonadotropin concentration was superior to the triple screen (area under the curve, 0.9337 vs 0.7887; P =.02). The substitution of urinary hyperglycosylated human chorionic gonadotropin concentration for serum human chorionic gonadotropin concentration in the triple screen resulted in a 91.7% sensitivity at a 10.0% false-positive rate, versus a 54.2% sensitivity for the traditional triple screen at the same false-positive rate. CONCLUSION: The performance of urinary hyperglycosylated human chorionic gonadotropin concentration was statistically superior to that of the serum triple screen in a high-risk population. The use of urinary hyperglycosylated human chorionic gonadotropin concentration as an alternative test or substitution of this measurement for serum human chorionic gonadotropin concentration in the triple screen would improve diagnostic accuracy and address many current concerns related to the triple screen.

Long-term outcome in twin-twin transfusion syndrome treated with serial aggressive amnioreduction.

OBJECTIVE: The purpose of this study was to determine long-term outcomes among pregnancies complicated by twin-twin transfusion syndrome and treated in a tertiary center with serial aggressive amnioreduction. STUDY DESIGN: Thirty-three pregnancies with a diagnosis of twin-twin transfusion syndrome were treated with > or =1 amnioreduction. The perinatal outcome was assessed according to 15 parameters, whereas the main outcome at age > or =2 years was the absence of cerebral palsy. RESULTS: Gestational age at diagnosis ranged from 14.5 to 33 weeks' gestation (median, 20.6 weeks' gestation), whereas gestational age at delivery was between 18.5 and 37 weeks' gestation (median, 30.5 weeks' gestation). The number of amnioreductions per pregnancy ranged from 1 to 15 (median, 2). At initial examination hydrops of the recipient and absence of the end-diastolic velocity of the umbilical artery in one of the twins were associated with poor prognosis. Fifty-one (77%) twins were born alive. At 24 months after birth both infants from 57% of the pregnancies (19/33) were alive, whereas at least one infant from 70% of the pregnancies (23/33) was alive. Thirty-three infants (78% of the survivors) were older than 36 months at last follow-up. Cerebral palsy was diagnosed in 2 of 42 infants (4.7%). One of the affected infants was born after the fetal death of the cotwin; the other infant was born with congenital cardiac malformations. CONCLUSIONS: In the group of fetuses in which both twins were delivered alive after 27 weeks' gestation without congenital malformations and survived the neonatal period, no major neurologic handicaps developed in any of the infants. At initial examination both hydrops of the recipient and absence of end-diastolic flow velocity waveforms of the umbilical artery in one of the twins were poor prognostic signs.

Urine hyperglycosylated hCG plus ultrasound biometry for detection of down syndrome in the second trimester in a high-risk population.

OBJECTIVE: To evaluate measurement of levels of urine hyperglycosylated hCG, a form of hCG with abnormally branched oligosaccharide side chains, in conjunction with ultrasound biometry for Down syndrome risk prediction in an at-risk group. METHOD: We prospectively measured urine hyperglycosylated hCG levels, humeral length, and nuchal thickness in women who had second-trimester amniocentesis. Urine hyperglycosylated hCG levels were measured by a two-step enzyme-immunometric assay using monoclonal antibody beta152. Humeral length, nuchal thickness, and hyperglycosylated hCG values were expressed as multiples of the median, and the Down syndrome screening efficiency of the three analytes plus age was determined. A receiver operating characteristic (ROC) curve was generated, and the area under the curve was used to assess the Down syndrome screening performance of the algorithm. RESULTS: There were 23 cases of Down syndrome among 1016 singleton pregnancies. Mean gestational age (+/- standard deviation) was 16.1 +/- 1.2 weeks at the time of amniocentesis. Mean maternal age was 37.1 +/- 3.2 years. Biometry and measurement of hyperglycosylated hCG levels had a 91.3% detection rate at a 3.2% false-positive rate and a 100% detection rate at a 10.7% false-positive rate. The area under the ROC curve was 0.986 (P <.001), and that for measurement of hyperglycosylated hCG levels plus age was 0.941 (P <.001). The area under the curve was significantly larger with combined biochemical and biometry markers compared with measurement of hyperglycosylated hCG levels plus age alone (P <.02), proving that the former was superior to the latter. CONCLUSION: A new Down syndrome biochemical marker combined with ultrasound biometry had a high screening efficiency in a high-risk group. All cases of Down syndrome in this study population would have been detected at an amniocentesis rate of less than 10.7%. Our results appear superior to those found with other second-trimester algorithms. The combination is promising as an alternative to "automatic" genetic amniocentesis in women of advanced maternal age and other high-risk groups.

Splenic artery Doppler peak systolic velocity predicts severe fetal anemia in rhesus disease.

OBJECTIVE: We sought to determine whether main splenic artery Doppler peak systolic velocity predicts severe anemia in the rhesus-alloimmunized fetus. STUDY DESIGN: Splenic artery Doppler peak systolic velocity was obtained before cordocentesis in rhesus-alloimmunized fetuses. Normative values for mean peak systolic velocity based on gestational age were obtained cross-sectionally from a separate group of 144 normal fetuses. The peak systolic velocity values in the study group were expressed as multiples of the median for gestation, and threshold values were used as a screening test for severe anemia. The hemoglobin deficit was defined as mean hemoglobin for gestation minus measured hemoglobin. A hemoglobin deficit value of > or =5 g/dL was used to define severe anemia. We used the peak systolic velocity to screen for severe anemia in the overall study group and the subgroups with or without prior transfusions. RESULTS: The study population consisted of 26 singleton nonhydropic fetuses in which cordocentesis and Doppler measurements were performed on a total of 55 occasions. The mean gestational age and standard deviation at cordocentesis was 29.6 +/- 4.0 weeks. Severe anemia was noted in 20% of fetal cord blood specimens obtained. On the basis of a receiver operating characteristic curve, a peak systolic velocity of > or =1.4 multiples of the median had a detection rate of 100%, with a false-positive rate of 20.8% in the subgroup with no prior transfusion (relative risk, 4.8; 95% confidence interval, 2.2-10.5). For peak systolic velocity threshold of > or =1.50 multiples of the median, corresponding values in the group with one prior transfusion were 80% and 12.5%, respectively (relative risk, 2.5; 95% confidence interval, 1.2-5.3). There was no risk of severe anemia with a peak systolic velocity below the median for gestation. CONCLUSION: Fetal hydrops is rare, with a hemoglobin deficit of <5 g/dL. In the first such report the main splenic artery peak systolic velocity was noted to be a strong predictor of severe anemia. For the overall population, all such instances could be diagnosed while cordocentesis was performed 22.7% of the time. There is no risk of severe anemia with Doppler peak systolic velocities below the median for gestational age. The measurement is easily obtained and should be investigated as a clinical tool for minimizing the necessity for cordocentesis.

Maternal urine beta-core hCG fragment level and small for gestational age neonates.

OBJECTIVE: To determine whether second-trimester urine beta-core fragments of hCG predict small for gestational age (SGA) neonates. METHODS: Spot urine beta-core levels were measured in 733 nonhypertensive women with singleton pregnancies who presented for amniocentesis and had karyotypically normal fetuses. The beta-core level was standardized to urine creatinine and expressed as multiples of the median. The area under a receiver operating characteristics curve was used to determine the screening efficiency of the urine analyte for prediction of small for gestational age (SGA) births. In a subgroup of cases, serum markers (alpha-fetoprotein [AFP], hCG, and unconjugated estriol) were compared using stepwise regression analysis to urine beta-core fragment for SGA prediction. RESULTS: There were 23 (3.0%) SGA neonates. The mean +/- standard deviation (SD) gestation at urine collection was 16.4 +/- 1.3 weeks and collection to delivery interval was 23.0 +/- 2.2 weeks. Mean beta-core (+/- SD) fragment levels were significantly higher in those who later had SGA infants compared with appropriately grown infants (2982.8 ng/mg creatinine versus 1447.4 ng/mg creatinine, P <.001). Stepwise logistic regression found that urine beta-core fragment and serum AFP were the only significant predictors of SGA, with statistically significant chi(2) values (P <.001 and P =.038, respectively). The urine analyte was significantly superior. Second-trimester urine beta-core fragment had a 78.3% sensitivity and 70% specificity for SGA prediction. Exclusion of preeclamptic cases resulted in a sensitivity of 84.2% and a specificity of 71.2%. CONCLUSION: Second-trimester elevated maternal urine beta-core fragment of hCG predicted SGA infants, and was superior to other serum analytes in that prediction.

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses.

BACKGROUND: Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. METHODS: We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. RESULTS: Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent. CONCLUSIONS: In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: A new basis for gestational Down syndrome screening.

BACKGROUND: Serum human chorionic gonadotropin (hCG) and hCG free beta-subunit tests are used in combination with unconjugated estriol and alpha-fetoprotein in the triple screen test, and with the addition of inhibin-A in the quadruple marker test for detecting Down syndrome in the second trimester of pregnancy. These tests have a limited detection rate for Down syndrome: approximately 40% for hCG or free beta-subunit alone, approximately 60% for the triple screen test, and approximately 70% for the quadruple marker test, all at 5%, or a relatively high, false-positive rate. New tests are needed with higher detection and lower false rates. Hyperglycosylated hCG (also known as invasive trophoblast antigen or ITA) is a new test. It specifically detects a unique oligosaccharide variant of hCG associated with Down syndrome pregnancies. We evaluated this new Down syndrome-directed test in prenatal diagnosis. METHODS: Hyperglycosylated hCG was measured in urine samples from women undergoing amniocentesis for advanced maternal age concerns at 14-22 weeks of gestation, 1448 with normal karyotype and 39 with Down syndrome fetuses. RESULTS: The median hyperglycosylated hCG value was 9.5-fold higher in Down syndrome cases (9.5 multiples of the normal karyotype median). The single test detected 80% of Down syndrome cases at a 5% false-positive rate. Urine hyperglycosylated hCG was combined with urine beta-core fragment (urine breakdown product of serum hCG free beta-subunit), serum alpha-fetoprotein, and maternal age-related risk. This urine-serum combination detected 96% of Down syndrome cases at a 5% false-positive rate, 94% of cases at a 3% false-positive rate, and 71% of cases at a 1% false-positive rate. These detection rates exceed those of any previously reported combination of biochemical markers. CONCLUSIONS: Hyperglycosylated hCG is a new base marker for Down syndrome screening in the second trimester of pregnancy. The measurement of hyperglycosylated hCG can fundamentally improve the performance of Down syndrome screening protocols.

Elevated maternal urine level of beta-core fragment of human chorionic gonadotropin versus serum triple test in the second-trimester detection of down syndrome.

OBJECTIVE: This study was undertaken to compare the Down syndrome screening efficiency of elevated maternal urine level of the beta-core fragment of human chorionic gonadotropin with that of the traditional serum triple test. STUDY DESIGN: Urinary beta-core fragment and serum analyte levels were measured prospectively in women with singleton pregnancies who were undergoing second-trimester genetic amniocentesis. Urinary analyte levels were measured within a week of specimen collection. In some cases only alpha-fetoprotein was measured initially and human chorionic gonadotropin and unconjugated estriol levels were subsequently determined from the stored serum specimens. The Down syndrome screening efficiency of urinary concentration of beta-core fragment plus maternal age was compared with that of the traditional triple test. Receiver operating characteristic curves were generated for each algorithm and the areas under the curves were compared to determine which algorithm was superior. RESULTS: There were a total of 926 study patients, of whom 21 (2.3%) carried fetuses with Down syndrome. The mean (+/-SD) gestations at amniocentesis were 16.6 +/- 1.5 weeks for the fetuses without Down syndrome and 17.7 +/- 2.3 for the fetuses with Down syndrome. A total of 539 women (4 of whom carried fetuses with Down syndrome) had serum alpha-fetoprotein alone measured initially. Urinary concentration of beta-core fragment had a 61.9% detection rate with a 4.9% false-positive rate for Down syndrome, whereas the values for the triple screen were 57. 1% and 11.2%, respectively. The areas under the receiver-operating characteristic curves were 0.8744 for elevated urinary beta-core fragment level and 0.7504 for the triple screen (P =.1116). When the false-positive rate was fixed at an ideal threshold value (

Endometrial adenocarcinoma in pregnancy.

OBJECTIVE: The coexistence of endometrial adenocarcinoma and pregnancy is rare. Most cases are discovered in the first trimester due to irregular bleeding or spontaneous abortion. CASE: A 44-year-old woman, gravida 3, para 2, was admitted due to abnormal vaginal bleeding. After complete history, physical examination, and laboratory evaluation, she was diagnosed with spontaneous abortion and underwent a suction curettage. Pathological examination of the tissue included chorionic villi and an area of atypical hyperplasia and endometrial cancer. CONCLUSION: Recent association between first-trimester spontaneous abortions and subsequent endometrial cancer makes these rare cases of concurrent endometrial cancer and first trimester of pregnancy attractive in that they may disclose insights into the pathophysiology of hormone-dependent cancers.

Urinary screening tests for fetal Down syndrome: I. Fresh beta-core fragment.

Variable results have been reported using urine beta-core fragment as a marker for fetal Down syndrome. Initial studies by Cuckle et al. (1994) and Canick et al. (1995) indicated that beta-core fragment was an outstanding marker, detecting >80 per cent of Down syndrome cases. Since these reports, widely varying results have been published, indicating between 20 per cent and 66 per cent detection of cases at 5 per cent false-positive rate. The wide variation in the reported data has led to a loss of enthusiasm for this marker as a useful test for Down syndrome screening. Here we report the results of a three-year prospective study in which urine samples were collected daily from women undergoing fetal karyotype analysis for advanced maternal age. Samples were tested within one week of collection and then frozen. We also investigated the likely causes of the variability observed in beta-core fragment data. We collected 1157 urine samples over 955 days. Beta-core fragment levels were measured. A regression line was calculated for the weekly medians of the 1134 control samples and multiples of the control median (MoM) were determined. The median MoM for the controls was 1.0 and the logarithmic standard deviation (log SD) was 0.41. The median MoM for the 23 Down syndrome cases was 5.44 and the log SD was 0.45. Over the study period, 65 per cent of Down syndrome cases exceeded the 95th centile of the control group. The median MoM of control samples and the proportion of Down syndrome cases detected by the test was relatively constant during the study period. The unaffected cases were divided into three equal divisions, corresponding to approximately the first, second and third year of sample collection. No trend was found in the median control MoM values in three sample collection periods (r2=0.04). A similar number of cases exceeded the 95th centile of control samples in the three sample collection periods, 63 per cent, 66 per cent and 66 per cent. Consistent results were indicated during the three years of sample testing. Levels of total oestriol were determined in urine samples and MoM statistics derived. The median oestriol level in Down syndrome cases was 0.59 MoM. Only 12 per cent of cases had MoM levels below the fifth centile. Gaussian models were prepared combining biochemical data and maternal age distribution. While beta-core fragment by itself detected 65 per cent of Down syndrome cases, beta-core fragment modelled with maternal age detected 66 per cent, and modelled with age and total oestriol levels detected 82 per cent of cases at 5 per cent false-positive rate. At the completion of the study, we thawed and reassayed 20 random urine samples (10 control and 10 Down syndrome) collected at different times during the study period. While the control samples (74-1700 ng/ml) had slightly increased values when reassayed (mean value 137 per cent of original prospective value), the Down syndrome samples (360-20,500 ng/ml) all had decreased values when reassayed (mean=53 per cent, t-test, controls versus cases, p = 0.0003). The Down syndrome samples were decreased to between 93 per cent and 12 per cent of the original value. A relationship was identified between the magnitude of the original beta-core fragment value and the change in immunoreactivity when reassayed (r2=0.998). The higher the initial beta-core fragment value the greater the loss of immunoreactivity. We considered the possibility that the beta-core fragment molecules aggregate upon storage in the freezer. We repeated the assay of the 20 samples after treatment with a high salt buffer. Down syndrome samples recovered half of the lost beta-core fragment immunoreactivity (mean increase in beta-core fragment levels 56 per cent, t-test, controls versus cases, p=0.004). We infer that aggregation of beta-core fragment upon storage interferes with beta-core fragment measurements. This may be the cause of the poor beta-core fragment screening performance reported using sto

Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG.

Hyperglycosylated hCG is a form of hCG with more complex oligosaccharide side chains. A specific immunoassay was developed to measure hyperglycosylated hCG. Levels were measured in urine samples from 1157 women between 11 to 22 weeks of gestation, undergoing genetic analysis because of advanced maternal age. Values were normalized to urine creatinine concentration and plotted against gestational age, median values were determined and multiples of the control median (MoM) calculated. The median MoM and log standard deviation (log SD) of the 1134 control samples was 1.0 and 0.47, and of the 23 Down syndrome cases was 7.8 and 0.48, respectively. This indicated a 7.8-fold increase in hyperglycosylated hCG levels in Down syndrome cases. In the accompanying article, a stability problem was found with beta-core fragment measurements in frozen urine samples. In anticipation of similar problems, nine urine samples were tested for hyperglycosylated hCG fresh and after storage in the freezer. No clear difference was found in hyperglycosylated hCG values. In addition, no trend was found in hyperglycosylated hCG MoM values or in Down syndrome detection rates in urine samples stored for one, two or three years in the freezer. Samples were split into five equal groups according to creatinine concentration. A trend was observed, hyperglycosylated hCG MoM values decreasing with advancing creatinine concentration (1.77, 1.08, 1.01, 0.73 and 0.60 at 0.25, 0.50, 0.79, 1.11 and 1.73 mg/ml, respectively). An error was noted. This was corrected with a regression equation. After correction, the median MoM and log SD of the control samples was 1.0 and 0.44, and of Down syndrome samples was 7.3 and 0.42, respectively. Correction of this error, while reducing the elevation of Down syndrome cases, tightened the spread of samples. Samples were ranked and centiles determined. 18 of 23 Down syndrome cases (78 per cent) exceeded the 95th centile of the control population. ROC analysis indicated 79 per cent detection at 5 per cent false-positive rate. Urine samples were collected during two periods of gestation, an early period (11th to 14th completed week) and the period when chemical screening is normally performed (15th to 21st week). ROC analysis indicated 80 per cent and 78 per cent detection rates, respectively, at 5 per cent false-positive rate, in the two gestational periods. Hyperglycosylated hCG values were modelled with beta-core fragment values, total oestriol values and maternal age. ROC analysis indicated 97 per cent detection rate at 5 per cent false-positive rate. This detection rate and this level of Down syndrome and control patient discrimination surpasses that of any other serum, urine or ultrasound screening protocol. Hyperglycosylated hCG should be considered as a new screening test for aneuploid pregnancies, with the potential of detecting almost all cases of Down syndrome. Evaluation is needed by other centres in order to bring hyperglycosylated hCG into clinical practice.