Influence of Mifepristone in Induction Time for Terminations in the Second and Third Trimester.

Termination of pregnancy after the first trimester is generally carried out by medical induction. Question: The aim of this study is to investigate the effect of mifepristone before administration of the prostaglandin derivative on induction time. Material and Methods: We analysed 333 medically indicated terminations after the first trimester under the terms of § 218 a Para. 2 of the German Criminal Code, in which the prostaglandin derivatives misoprostol, gemeprost or dinoprostone were administered with or without pre-treatment with 600 mg of mifepristone. The time interval between the initial administration of prostaglandin and delivery was investigated. Using uni- and multivariate regression analysis, the effect of maternal age, body mass index, gravidity and parity, previous Caesarean sections, gestational age and the induction regimen on the induction time were analysed. Results: The average induction time was significantly shortened with mifepristone (15.1 ± 11.9 hours with mifepristone vs. 25.3 ± 24.2 hours without mifepristone [p < 0.001]). The combination of mifepristone and misoprostol was most frequently used and proved to be the most effective regimen, reducing the induction period to 13.6 ± 10.3 hours. Besides pre-treatment with mifepristone, gestational age and a history of delivery without Caesarean section were significant influencing factors in reducing the induction time. Conclusion: The induction interval can be significantly shortened by the prior administration of mifepristone. The combination of mifepristone and misoprostol or gemeprost is the most effective regimen for the medical termination of pregnancy.

Optimal caliper placement: manual vs automated methods.

OBJECTIVE: To examine the inter- and intra-operator repeatability of manual placement of callipers in the assessment of basic biometric measurements and to compare the results to an automated calliper placement system. METHODS: Stored ultrasound images of 95 normal fetuses between 19 and 25 weeks' gestation were used. Five operators (two experts, one resident and two students) were asked to measure the BPD, OFD and FL two times manually and automatically. For each operator, intra-operator repeatability of the manual and automated measurements was assessed by within operator standard deviation. For the assessment of the interoperator repeatability, the mean of the four manual measurements by the two experts was used as the gold standard.The relative bias of the manual measurement of the three non-expert operators and the operator-independent automated measurement were compared with the gold standard measurement by means and 95% confidence interval. RESULTS: In 88.4% of the 95 cases, the automated measurement algorithm was able to obtain appropriate measurements of the BPD, OFD, AC and FL. Within operator standard deviations of the manual measurements ranged between 0.15 and 1.56, irrespective of the experience of the operator.Using the automated biometric measurement system, there was no difference between the measurements of each operator. As far as the inter-operator repeatability is concerned, the difference between the manual measurements of the two students, the resident, and the gold standard was between -0.10 and 2.53 mm. The automated measurements tended to be closer to the gold standard but did not reach statistical significance. CONCLUSION: In about 90% of the cases, it was possible to obtain basic biometric measurements with an automated system. The use of automated measurements resulted in a significant improvement of the intra-operator but not of the inter-operator repeatability, but measurements were not significantly closer to the gold standard of expert examiners.

Comparison of three methods of cervical measurement in the first trimester: single-line, two-line, and tracing.

OBJECTIVES: To compare three methods of cervical length measurements using ultrasound in the first trimester: single-line, two-line, and tracing. METHODS: Images appropriate for cervical length measurements were obtained using transvaginal ultrasound between 11 + 0 and 13 + 6 weeks' gestation. The cervix was measured on stored images using three methods: a single straight line, two segments (two-line method), and by tracing the distance along the cervical canal. Results were compared for intraoperator repeatability and interoperator variability. The degree of the cervical curvature was measured. RESULTS: The mean cervical measurement using the single-line measurement was 32.8 (SD 4.4) mm. The mean cervical length was essentially the same using the two-line and tracing measurement: 34.4 (SD 4.7) mm and 34.5 (SD 4.7) mm, respectively. Both intra- and interoperator agreement was high. The degree of curvature of the cervical canal was variable, with a resultant variability in the difference between the single straight line measurement and the other two types of measurement. CONCLUSIONS: Using stored images, each of the measurement techniques is highly reproducible. Both the two-line and the tracing methods yield larger measurements than the single-line technique. Therefore, it appears that in select cases the straight line measurement significantly underestimates the actual cervical length.

Prefrontal space ratio in second- and third-trimester screening for trisomy 21.

OBJECTIVE: To evaluate the prefrontal space ratio (PFSR) in second- and third-trimester euploid fetuses and fetuses with trisomy 21. METHODS: This was a retrospective study utilizing stored mid-sagittal two-dimensional images of second- and third-trimester fetal faces that were recorded during prenatal ultrasound examinations at the Department of Prenatal Medicine at the University of Tuebingen, Germany and at a private center for prenatal medicine in Nuremberg, Germany. For the normal range, 279 euploid pregnancies between 15 and 40 weeks' gestation were included. The results were compared with 91 cases with trisomy 21 between 15 and 40 weeks. For the ratio measurement, a line was drawn between the leading edge of the mandible and the maxilla (MM line) and extended in front of the forehead. The ratio of the distance between the leading edge of the skull and the leading edge of the skin (d1) to the distance between the skin and the point where the MM line was intercepted (d2) was calculated. The PFSR was determined by dividing d2 by d1. RESULTS: In the euploid and trisomy 21 groups, the median gestational age at the time of ultrasound examination was 21.1 (range, 15.0-40.0) and 21.4 (range, 15.0-40.3) weeks, respectively. Multiple regression analysis showed that PFSR was independent of maternal and gestational age. In the euploid group, the mean PFSR was 0.97 ± 0.29. In fetuses with trisomy 21, the mean PFSR was 0.2 ± 0.38 (P < 0.0001). The PFSR was below the 5(th) centile in 14 (5.0%) euploid fetuses and in 72 (79.1%) fetuses with trisomy 21. CONCLUSION: The PFSR is a simple and effective marker in second- and third-trimester screening for trisomy 21.

A new formula for optimized weight estimation in extreme fetal macrosomia (≥ 4500 g).

PURPOSE: To develop and to evaluate a specific sonographic weight formula for fetuses with extreme macrosomia (≥ 4500 g). MATERIALS AND METHODS: A statistical estimation technique known as "gradient boosting with component-wise P-splines" was applied to a group of 174 fetuses with a birth weight (BW) ≥ 4500 g. Each fetus underwent an ultrasound examination with complete biometric parameters within 7 days of delivery. The exclusion criteria were multiple pregnancy, intrauterine death, and major structural or chromosomal anomalies. A new formula was derived using the obtained data and was then compared to currently available equations for estimating weight in the macrosomic fetus. RESULTS: The new formula is: log10 (EFW) = 3.6687781710 - 0.0003230278 × (BPD - 100.4080) - 0.0000843433 × (BPD - 100.4080)^2 + 0.0007281281 × (OFD - 120.6322) + 0.0000664323 × (OFD - 120.6322)^2 + 0.000000001794019 × exp(ATD - 120.1552) + 0.0005946974 × (APAD - 121.2069) - 0.0000210137 × (APAD - 121.2069)^2 - 0.000003318 × (APAD - 121.2069)^3, where EFW is the estimated fetal weight, BPD is the biparietal diameter, OFD is the occipitofrontal diameter, ATD is the abdominal transverse diameter, and APAD is the abdominal anteroposterior diameter. The new formula proved to be superior to other established equations, showing the lowest mean absolute percentage error (MAE 2.506), the smallest variance regarding the signed percentage error (SPE) (SD 3.376), and the best distribution of absolute percentage errors within prespecified error bounds. CONCLUSION: This new formula significantly improves weight estimation in fetuses with extreme macrosomia.

[First-trimester screening for trisomies 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13]. / Screening auf Trisomie 18 und Trisomie 13 durch das kombinierte Anwenden der Risiko-Algorithmen für Trisomie 21, 18 und 13.

PURPOSE: Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13. MATERIALS AND METHODS: First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free ß-hCG was assessed in 39 ,004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm. RESULTS: The study population consisted of 38 ,751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free ß-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %. CONCLUSION: Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %.

Fetal weight estimation in extreme macrosomia (≥ 4,500 g): comparison of 10 formulas.

PURPOSE: The aim of this retrospective study was to compare the accuracy of 10 commonly used weight estimation formulas in a group of fetuses with extreme macrosomia ( ≥ 4 ,500 g). MATERIALS AND METHODS: Ten formulas were evaluated in a group of 174 fetuses with a birth weight (BW) ≥ 4 ,500 g. Each fetus underwent ultrasound examination with complete biometric parameters within 7 days of delivery. The accuracy of the different formulas for fetal weight estimation (EFW) was compared by mean percentage error (MPE), median of the absolute percentage error (MAPE), the "limits-of-agreement" method and the percentage of EFW falling within the 10 % range of the true birth weight. RESULTS: MPE showed the largest deviation from zero with the Schild formula (MPE - 15.43 %) and the Shepard formula (MPE + 6.08 %) and was closest to zero with the Hadlock II formula (MPE - 5.34 %). The MPE of all formulas showed significant bias when compared to zero. All tested formulas, except the Shepard and Shinozuka equations, significantly underestimated fetal weight. The lowest MAPE was found for the Merz formula (7.23 %). The Hadlock II formula obtained the highest percentage of EWF within the 10 % range of the true birth weight (66.1 %). CONCLUSION: Exact weight estimation in extreme macrosomia remains an unsolved problem, and can therefore only conditionally provide a sufficient basis for clinical decision processes.

Prenatal evaluation of the position of the fetal conus medullaris.

OBJECTIVES: To determine the position of the fetal conus medullaris during pregnancy in relation to the last vertebral body and to examine its use in detecting skin-covered spinal dysraphism. METHODS: This was a retrospective study involving 300 consecutive ultrasound examinations between 15 weeks of gestation and term. Two operators independently assessed images of the spine to determine whether the conus medullaris and the last vertebral body could be visualized in a single image in a midsagittal plane. The distance between these two landmarks (the conus distance) was measured twice by both operators who were not aware of any previous measurements. Intra- and interobserver variability was assessed by 95% limits of agreement. Linear regression analysis was used to determine the relevant contributors to the conus distance and a normal range was computed based on the best-fit model. The normal results were compared with five cases of prenatally detected skin-covered spinal dysraphism. RESULTS: In 84.7% of the 300 cases, both operators were able to visualize the conus medullaris and the last vertebral body. Ninety-five percent limits of agreement for the intraobserver variability in measurement of conus distance were ± 1.9 mm. For the interobserver variability, they were - 3.7 and 2.5 mm. We found a linear relationship between conus distance and gestational age, biparietal diameter and abdominal circumference. The strongest relationship was observed for femur length (conus distance = - 8.2 + femur length (mm)). In the five abnormal cases, conus distance was well below the 5(th) percentile. CONCLUSIONS: Determination of conus distance allows for an objective and feasible assessment of the conus medullaris position. This parameter promises to be useful in the prenatal detection of skin-covered spinal dysraphism.

Effects of combination of intrathecal lidocaine and two doses of intrathecal midazolam on post-operative pain in patients undergoing herniorrhaphy: a randomized controlled trial.

Assessment of the effect of combination of intrathecal midazolam and lidocaine on postoperative pain was the aim of this study. This randomized controlled trial was performed during 2007 in a teaching hospital of Arak University of Medical Sciences. Forty five male patients who were candidates for elective inguinal herniorrhaphy entered the study and randomly divided into three groups of control (lidocaine 5% plus normal saline), M 0.5 (lidocaine 5% and midazolam 0.5 mg) and M 1.0 (lidocaine 5% and midazolam 1 mg) according intrathecal solution injected for spinal anesthesia. Mean arterial blood pressure, heart rate, post-operative pain, narcotic requirements and complications (nausea, vomiting, pruritic, headache, hypotension and bradycardia) were recorded. The severity of post-operative pain was lowest in M 1.0 group in all postoperative measurements except at 2 h after operation. With regard of complications, only there was significant difference in vomiting between three groups which had the highest frequency in M 0.5 group. No severe hypotension was seen; though, bradycardia occurred in one patient in M 0.5 group which needed treatment. Present findings suggest that administration of intrathecal midazolam (especially 1 mg) together with lidocaine is effective in reducing post-operative pain in patients undergoing open inguinal herniorrhaphy and is not associated with adverse effect.

Vascularized bone marrow transplantation (VBMT): induction of stable mixed T-cell chimerism and transplantation tolerance in unmodified recipients.

In this preliminary report, our model of VBMT across a semiallogeneic barrier consistently brings about antigen-specific host tolerance with absence of GVHD in the majority of recipients. No immunologic or radiologic intervention was utilized. These results emphasized a potentially important mechanism for low-level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent of immune suppressive effects due to irradiation or immunopharmacologic intervention.

Development of stable mixed T cell chimerism and transplantation tolerance without immune modulation in recipients of vascularized bone marrow allografts.

A consistent majority (62.5%) of immunologically unmodified rat recipients transplanted with vascularized hind-limb bone marrow allografts across a semiallogeneic transplant barrier developed tolerance with absence of graft-versus-host disease. A minority of recipients (37.5%) demonstrated lethal GVHD. Transplantation tolerance in the majority was associated with the induction of stable low-level mixed T cell chimerism, including donor CD5+, CD4+, and CD8+ lymphocytes. Chimeras were specifically immune nonresponsive to host alloantigenic determinants. These results emphasized a potentially important mechanism for low-level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent of immune suppressive effects due to irradiation or immunopharmacologic intervention. These vascularized bone marrow transplantation (VBMT) results may establish the experimental foundation for a novel approach to stem cell transfer and bone marrow transplantation.