Pitfalls of ultrasonographic yolk sac measurement.

PURPOSE: Novel aneuploidy screening has been suggested for measuring the yolk sac during very early pregnancy. However, in a pilot study the measured diameters differed up to 29 % from the overall average. The aim of this study was to analyze the impact of image magnification on yolk sac measurement. MATERIALS AND METHODS: From November 3, 2009 to July 28, 2010, 119 yolk sac measurements were performed. During each examination, each yolk sac was examined once with standard image magnification and once by live scan zoom. RESULTS: The measurement values were 5 % smaller in the standard image. The mean relative ratio (RR), median RR, and standard deviation (SD) were 0.951, 0.950, and 0.103 mm, respectively (95 % CI 0.744 to 1.158 mm). Regarding absolute differences, the mean, median, and standard deviation were -0.222 mm, -0.220 mm, and 0.473 mm, respectively, (95 % CI -1.169 to + 0.725 mm). With standard zoom (magnified images), the SD was 1.142 mm (1.099 mm). CONCLUSION: Five criteria should be regarded for optimal image settings: image magnification during live scan, optimal gain setting, enhanced gamma level, median section plane, and out-to-out caliper placement.

Age-independent first trimester screening for Down syndrome: analysis of three modified software programs with 6,508 pregnancies.

BACKGROUND: The conventional first trimester screening (FTS) method integrates maternal age into risk calculation. It was suggested that this concept increases the false-positive rate in older, and the false-negative rate in younger mothers. MATERIALS AND METHODS: Six thousand five hundred and eight combined FTS with known fetal outcome underwent regular risk calculation with the software programs Pia fetal database (PIA) (GE-ViewPoint, GE Medical Systems), prenatal risk calculation (PRC) (Version 1.0.61, gmt/nexus), and JOY (Version 2.1, PET software). The results were mathematically modified as if generated with age-independent software (PIA(mod), PRC(mod), and JOY(mod)). RESULTS: 17 of 40 trisomy 21 cases were present in women younger than 35. A right shift in the mean maternal age of false-negative cases occurred in all programs (PIA: 30.00, PIA(mod): 32.00, PRC: 30.00, PRC(mod): 32.25, JOY: 30.00, JOY(mod): 34.50). The overall false-positive rate declined by -40.03% (PIA(mod)), -38.64% (PRC(mod)), and -37.50% (JOY(mod)) and in women over 35 (40) years by -72.37, -73.45, and -73.20% (-89.04, -90.33, and -90.56%), being then as high as in the other age groups. CONCLUSION: First trimester screening would become reasonable in women over 40 years. However, women over 35 would also be more often affected by false-negative results. The implications of a concept adaptation should be analyzed in a large prospective study.

[Prospective performance evaluation of first trimester screenings in Germany for risk calculation through http://www.firsttrimester.net]. / Prospektive Testleistungsbewertung des Ersttrimester Screenings in Deutschland bei Risikoberechnung über http://www.firsttrimester.net.

BACKGROUND: In 2008, 2 351 first trimester screenings were calculated by a newly developed internet database ( http:// www.firsttrimester.net ) to evaluate the risk for the presence of Down's syndrome. MATERIAL AND METHODS: All data were evaluated by the conventional first trimester screening according to Nicolaides (FTS), based on the previous JOY Software, and by the advanced first trimester screening (AFS). After receiving the feedback of the karyotype as well as the rates of the correct positives, correct negatives, false positives, false negatives, the sensitivity and specificity were calculated and compared. RESULTS: Overall 255 cases were investigated which were analysed by both methods. These included 2 cases of Down's syndrome and one case of trisomy 18. The FTS and the AFS had a sensitivity of 100%. The specificity was 88.5% for the FTS and 93.0% for the AFS. CONCLUSION: As already shown in former studies, the higher specificity of the AFS is a result of a reduction of the false positive rate (28 to 17 cases). As a consequence of the AFS with a detection rate of 100% the rate of further invasive diagnostics in pregnant women is decreased by having 39% fewer positive tested women.

Analysis of the distribution shift of detected aneuploidies by age independent first trimester screening.

INTRODUCTION: First trimester screening (FTS) became standard in non-invasive testing for chromosomal abnormalities in early pregnancy. The individual risk is calculated on the basis of a general background risk, which refers to the maternal age. A new method, Advanced Firsttrimester Screening (AFS) excludes the background risk in its algorithm. This study had the aim to analyze how the detection of aneuploidies is influenced by the in- or exclusion of the maternal age in the risk calculation. MATERIALS AND METHODS: The data of 15,228 first trimester screenings were recalculated with FTS and AFS. The study cohort was divided by age into nine groups and the numbers of detected cases were recorded according to the groups of age. RESULTS: Of 129 detected aneuploidies 90% got the same test results, disregarding whether risk assessment is performed including maternal age or not. FTS detected five aneuploidies at age 35 or older that were not recorded by AFS. AFS detected six aneuploidies that were not detected by FTS. Out of these, the oldest mother was 32 years old. DISCUSSION: When excluding the maternal age from risk calculation, the detection of aneuploidies showed a shift from older to younger women. Overall, the detection rate did not change significantly. However, the false positive rate was 25% lower with the exclusion of maternal age.

Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer.

Expression of the Bcl-2 protein confers resistance to chemotherapy-mediated apoptotic signals in patients with breast cancer. We investigated effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 messenger RNA (mRNA), down-regulates Bcl-2 protein translation and enhances antitumor effects of subtherapeutic chemotherapy doses. Within a phase I trial, we administered escalating doses of oblimersen (3, 5 or 7 mg/kg/day) as continuous infusion on days 1-7 in combination with standard-dose docetaxel (Taxotere), Adriamycin and cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with T2-4 tumors. Effects of oblimersen were evaluated in tumor biopsies and peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen and before TAC treatment by quantitative microfluidic real-time PCR. Read-outs consisted in measurement of Bcl-2 mRNA modulations and of 18 putative predictive markers. Two of 13 patients showed a diminution of Bcl-2 transcripts after 4 days of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate tissue because no qualified RNA could be isolated. Nevertheless, we demonstrated feasibility to process clinical samples and to obtain good quality RNA from tumor biopsies and indicated the potential of oblimersen to lower Bcl-2 mRNA in breast cancer.

Heterotopic pregnancy: simultaneous intrauterine and ectopic pregnancy following IVF treatment with the birth of a healthy child.

Although spontaneous simultaneous intrauterine and ectopic pregnancy was an extremely rare event in the past, it is increasingly being diagnosed since the rate of assisted reproduction technique (ART) gestations increased. Due to the serious consequences, delayed diagnosis should be prevented in order to salvage the viable intrauterine fetus and avoid maternal morbidity and mortality. This case report demonstrates that the pitfalls of the diagnosis of heterotopic pregnancy make early diagnosis difficult and the prevention of heterotopic pregnancies by single embryo transfer should be continuously discussed. The role of high resolution ultrasound scans and the importance of close monitoring of early pregnancies following ART are emphasized because early diagnosis of heterotopic pregnancy results in a similar perinatal outcome as singleton pregnancies.

Interobserver variability of the measurement of fetal nasal bone length between 11+0 and 13+6 gestation weeks among experienced and inexperienced sonographers.

PURPOSE: Examination of fetal nasal bone (NB) by ultrasound between 11 + 0 and 13 + 6 gestation weeks has been proposed as an additional tool in the detection of trisomy 21 and therefore its application and implementation are used in a broad range. The study aimed at evaluating the interobserver feasibility of the measurement of fetal nasal bone length in comparison with experienced and inexperienced sonographers. MATERIALS AND METHODS: The study population was comprised of women who chose to have first trimester screening (FTS) at the Fetal Medicine Unit of the University Medical School of Hannover. Two experienced (> 400 FTS examinations, sonographer 1 and 2) and one inexperienced sonographer (95 FTS examinations, sonographer 3) were asked to measure the nasal bone length consecutively and independently of each other. Statistical analysis was performed for any differences and variations in the results. RESULTS: The fetal profile was examined in 220 cases. The median nasal bone length by sonographer one was 2.4 cm, sonographer two 2.4 cm and sonographer three 2 cm. The differences between the results of sonographer 1 and 3 as well 2 and 3 were statistically significant. There were no significant variations between the results of sonographer 1 and 2. There was also no significant difference in the results concerning nuchal translucency and crown-rump length among the three examiners. CONCLUSION: The uncertainty and the difficulties of an inexperienced examiner with the presenting of the nasal bone, as shown by published data sets as well as by the variability of the measurement results of this study, with all the consequences in the risk calculation and counseling show that this tool should only be implemented by experienced and quality-controlled sonographers with a minimum amount of examinations. Because of its major impact in risk calculation and the importance of the nasal bone as a sonographic marker, documentation of the sonographer's skills is mandatory for the use of the nasal bones as an additional sonographic marker in first trimester screening.

Preliminary analysis of the new 'Prenatal Risk Calculation (PRC)' software.

OBJECTIVES: In February 2007, the "Fetal Medicine Foundation Germany (FMF-D)" introduced its new calculation software for First Trimester Screening (FTS), called "Prenatal risk calculation (PRC)". The aim of this study was to retrospectively investigate the test performance of PRC in comparison to the "NT module of the JOY software (JOY)". METHODS: A total of 3,516 combined first trimester screenings from 11 + 0 to 13 + 6 weeks of gestation were accomplished according to the FMF-standard. Adjusted risk calculation for aneuploidy was performed with PRC and JOY. RESULTS: A total of 2,202 complete data sets of singleton pregnancies were analyzed, including 10 trisomy 21 cases, 4 trisomy 18 cases, and 1 trisomy 13 case. Risk calculation with PRC and JOY showed highly significant results (P value<0.0001). JOY attained, at a cut-off of 1:300 (sensitivity 82.4%, false-positive rate 3.6%, positive predictive value 15.2%) and at a cut-off of 1:230 (82.4, 2.4, 21.2%), a better test performance in comparison to PRC (76.5, 7.1, 7.7% and 76.5, 5.3, 10.2%, respectively). The differences were highly significant (P value<0.0001). CONCLUSION: In this preliminary study, PRC demonstrated highly significant results in detecting aneuploidies in FTS. However, in comparison to JOY, its test performance was significantly inferior. A twice higher false positive rate would have doubled unnecessary invasive testing in a prospective setting. We therefore recommend a methodical revision of PRC.

Comparison of Prenatal Risk Calculation (PRC) with PIA Fetal Database software in first-trimester screening for fetal aneuploidy.

OBJECTIVES: In February 2007 new software, Prenatal Risk Calculation (PRC), for calculating the risk of fetal aneuploidy was introduced in Germany. Our aim was to investigate its test performance and compare it with that of the PIA Fetal Database (PIA) software developed and used by The Fetal Medicine Foundation. METHODS: Between 31 August 1999 and 30 June 2004 at the Women's Hospital of the Medical University of Hanover in Germany, 3120 singleton pregnancies underwent combined first-trimester screening at 11 + 0 to 13 + 6 weeks of gestation. Calculation of risk for fetal aneuploidy was computed prospectively using the PIA software. In a subsequent retrospective analysis, we recalculated risks for the 2653 of these datasets with known fetal outcome using the PRC software and compared the results. RESULTS: Of the 2653 datasets analyzed, 17 were cases of aneuploidy. At a cut-off of 1 : 230, for the detection of fetal aneuploidy, the respective sensitivity, false-positive rate and positive predictive value were 70.6%, 4.1% and 9.9% for PRC and 76.5%, 2.9% and 14.6% for PIA. At a cut-off of 1 : 300, the equivalent values were 70.6%, 5.6% and 7.5% for PRC and 76.5%, 4.0% and 11.0% for PIA. The differences in test performance between the two types of software were highly significant (P < 0.0001). DISCUSSION: The test performance of PRC was inferior to that of PIA, the sensitivity for detection of fetal aneuploidy being lower and the false-positive rate higher. Had PRC been employed prospectively in our study, 40% more women examined would have been offered unnecessarily an invasive procedure for fetal karyotyping.

How imprecise may the measurement of fetal nuchal translucency be without worsening first-trimester screening?

OBJECTIVE: First-trimester screening (FTS) has a trisomy 21 detection rate of about 90%. Despite profound training, the practically reached measurement quality of nuchal translucency (NT) is probably not optimal. This study investigated the impact of measurement errors on FTS. METHODS: The data on 10,116 combined FTSs were obtained in a multicenter study. Risk assessment was performed by the JOY software following the Nicolaides risk calculation principles. To investigate the impact of measurement errors, the NT values were artificially altered and the adjusted risks were recalculated. Test performance parameters were obtained and compared with the correct measurements. RESULTS: In this study 85 fetuses were genetically affected. The screening was wrongly inconspicuous in 12 cases and in 479 cases the FTS offered false-positive results. An assumed NT error of +/-0.1 mm already causes a highly significant change in the false-positive rate. A difference of -0.2 mm leads to a visible change in false negatives. DISCUSSION: This study demonstrates that even the smallest deviations will significantly affect the false-negative rate. The detection of really diseased fetuses is influenced at a -0.2-mm measurement error. Therefore the NT measurement has to be as precise as possible.

[Three-dimensional scatter plot analysis to estimate the risk of foetal aneuloidy]. / Dreidimensionale scatterplotanalyse zur risikoeinschätzung für fetale aneuploidien.

PURPOSE: First trimester screening (FTS) according to Nicolaides is now a worldwide established method for prenatal aneuloidy screening. An improvement was achieved by the "Advanced First Trimester Screening" (AFS). It was the aim of the current study to set up scatter plots from nuchal translucency (NT), Papp-A and fbeta-hCG, to derive likelihood ratios therefrom and to apply them to a test collective. We wanted to examine whether or nor the test performance of FTS could further be improved. MATERIAL AND METHODS: In a multicentre study 10 136 singleton pregnancies were recruited. Risk assessment for the presence of aneuploidies was performed by the Pia Fetal Database (PIA). In addition, all data were recalculated by the AFS module of the online platform www.firsttrimester.net . In a third step, a newly developed algorithm was utilised, in which the foetal parameters DeltaNT, Papp-A and fbeta-hCG were put into a three-dimensional scatter plot. The surrounding volume was segmentally divided and for each space the relation of the healthy to the affected foetuses found therein was determined. Furthermore, for all participiants of this study, the likelihood ratios were examinied at the segment according to the currently measured values. This method is designated as AFS-3D. RESULTS: Within the observed fetuses, 86 cases with aneuploidy were detected. By appropriate choice of the cut-off the sensitivities were found to be 83 % (PIA and AFS) and 82 % (AFS-3D), respectively, and do not differ significantly from each other. The specificity could be improved from 94 % (PIA) to 96 % (AFS) and was further advanced to 98 % by the AFS-3D method. At the same time the false positive rate was lowered from 654 (PIA) to 397 (AFS) and 228 (AFS-3D) cases, respectively. DISCUSSION: By means of the new AFS-3D method the same count of diseased fetuses was detected compared with prior screening tests. Simultaneously, expectant mothers were spared from unnecessary invasive diagnostics in 65 % of the cases. The choice of an altered cut-off or other volume shapes are feasible and should be examined in further studies.

Oblimersen combined with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment in primary breast cancer: final results of a multicentric phase I study.

BACKGROUND: Combining the Bcl-2 down-regulator oblimersen with cytotoxic treatment leads to synergistic antitumor effects in preclinical trials. This multicentric phase I study was carried out to evaluate maximum tolerated dose (MTD), safety and preliminary efficacy of oblimersen in combination with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment (NST) in primary breast cancer (PBC). METHODS: Previously untreated patients with PBC T2-4a-c N0-3 M0 received one cycle of docetaxel 75 mg/m(2), adriamycin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) administered on day 5 combined with escalating doses of oblimersen as a 24-h continuous infusion on days 1-7 followed by five cycles of combination of docetaxel, adriamycin and cyclophosphamide (TAC) without oblimersen every 3 weeks. Prophylactic antibiotic therapy and granulocyte colony-stimulating factor administration were used in all six cycles. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. RESULTS: Twenty-eight patients were enrolled (median age, 50 years; ductal-invasive histology, 68%; tumorsize 2-5 cm, 61%; grade 3, 43%; hormone receptor negative, 36%; Her2 positive 18%) and received oblimersen in a dose of 3 mg/kg/day (cohort I, nine patients), 5 mg/kg/day (cohort II, nine patients) and 7 mg/kg/day (cohort III, 10 patients) respectively. No dose-limiting toxicity occurred. Following oblimersen combined with TAC, the most severe toxicity was neutropenia [National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 1-2/3/4] which developed in 0/0/56% of patients (cohort I), 11/0/56% of patients (cohort II) and 20/20/50% of patients (cohort III). No febrile neutropenia occurred. Most common adverse events (all NCI-CTC grade < or = 2) were fatigue, nausea, alopecia, headache and flue-like symptoms observed in 78% (cohort I), 89% (cohort II) and 90% (cohort III) of patients. With increasing dose of oblimersen, a higher incidence of grade IV leukopenia and neutropenia was noted. At the MTD of 7 mg/kg/day of oblimersen, serious adverse events occurred in 40% of the patients. CONCLUSION: Oblimersen up to a dose of 7 mg/kg/day administered as a 24-h infusion on days 1-7 can be safely administered in combination with standard TAC on day 5 as NST in patients with PBC. The safety and preliminary efficacy warrants further evaluation of oblimersen in combination with every cycle of the TAC regimen in a randomized trial.

[Influence of circadian rhythm on fetal and maternal Doppler parameters--is a diurnal variation detectable?]. / Einfluss von zirkadianer rhythmik auf fetale und maternale Dopplerparameter--ist eine tageszeitliche veränderung nachweisbar?

INTRODUCTION: Doppler sonography is an established method in fetal medicine. Up to now a possible circadian rhythm of fetal and maternal Doppler parameters has only been insufficiently characterized and documented. This survey aimed at evaluating the significance of Doppler parameters with regard to diurnal variations. We have analyzed whether or not a circadian rhythm of fetal and maternal Doppler parameters is detectable. MATERIAL AND METHODS: A non-selected collective of 100 patients with a singleton pregnancy between the 20th and 39th week of gestation was examined with Doppler sonography at the Medical School of Hannover. Besides the Doppler sonography, which was performed at three fixed times a day, the maternal blood pressure was examined each time. Outcome parameters were resistance index (RI), pulsatility index (PI) and the maximum velocity (V (max)) of the A. umbilicalis, A. cerebri media and the Aa. uterinae as well as the maternal blood pressure. RESULTS: There were no significant differences for the RI, PI and V (max) of the Aa. uterinae for the whole collective, nor for the subgroups of maternal hypertonia, preeclampsia, notching and fetal growth restriction (IUGR). There were also no significant diurnal variations of the Doppler parameters for the fetal vessels. In particular, there were no differences in the measured Doppler parameters in comparison to the collective with unremarkable gravidity. In some subgroups statistical significance could be achieved, but due to the minor variations, no clinical importance has to be considered. CONCLUSION: A circadian rhythm of the Doppler parameters could not be confirmed in the examined collective. The time of the applied Doppler sonography on physiological conditions might represent a factor which does not affect the validity of the Doppler sonographic results. As a consequence a single Doppler examination at a freely chosen time seems to be sufficient to obtain a correct assessment of fetal and maternal blood perfusion. Further studies on larger collectives are necessary to evaluate the clinical importance of a possible circadian rhythm, especially in fetuses with pathological Doppler values.

Using "Degree of Extremeness" instead of "Multiples of Median" in first trimester risk assessment for Down syndrome-an improved method or just a gimmick in face of political motivations?

INTRODUCTION: The concept of first trimester Down syndrome screening based on (NT) nuchal translucency measurement was introduced by the Fetal Medicine Foundation (FMF), London, in the late 1990s. For Germany, the mandate of NT training and auditing was assigned to the newly established German branch of the FMF in 2002. In January 2007, following the organisational split between FMF London and FMF Germany, the FMF Germany released its own, novel calculation software ("Prenatal risk calculation", PRC), for this field. It is the aim of this study to compare the modified biochemical calculation method based on "Degree of Extremeness" (DoE) with the well-proven concept of "Multiple of Median" (MoM). MATERIALS AND METHODS: The fbeta-hCG and PAPP-A values of 266 first trimester examinations were categorised by gestational age, nicotine consumption and body weight. For each, a scatter plot and Pearson correlation was derived. As a second step, only patients with no nicotine consumption and a body weight between 55 and 65 kg were considered. The remaining 84 cases were again classified by gestational age and a statistical analysis was performed. RESULTS: The correlation of the DoEs with the respective MoM values was found to be quite good (r = 0.76, P < 0.01). After dividing the population by gestational age, the cohort of early pregnancies showed a steeper fss-hCG correlation curve than later stages. The examination regarding nicotine consumption showed no significant differences between smokers and non-smokers. In contrast, maternal body weight was found to have a marked influence. When only body weights between 55 and 65 kg were included and smokers were excluded, the Pearson correlations clearly converged. DISCUSSION: In this study, the utilisation of DoEs instead of MoMs was not clearly superior but it also did not seem to be inappropriate. However, it is most problematic to ignore evidently meaningful factors like body weight and ethnicity. It must also be considered risky to introduce a new calculation software to the market, when it is not clear whether the test performance is in fact comparable to established software concepts, especially in view of the fact that not only a new (unproven) database, but also a new (again unproven) algorithm is used in the PRC software. As the new program has not been evaluated yet, the test performance parameters should be validated urgently.

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

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

[Gestational diabetes under clinical conditions in aspired normoglycemia: investigation for correlation of blood glucose daily profiles and fetometric ultrasound parameters]. / Der Gestationsdiabetes unter klinischen Bedingungen bei angestrebter Normoglykämie: Korrelationsuntersuchungen zwischen maternalen Blutzuckertagesprofilen und fetometrischen Ultraschallparametern.

BACKGROUND: One of the therapeutic aims in gestational diabetes (GDM) is to prevent the development of fetal hypertrophy by adaptation of maternal glycemic control. Relating to this context, maternal blood glucose daily profiles and fetal biometry ultrasound parameters were analysed for a possible correlation. A special focus was given to the question as to whether a latency period exists for this possible connection. PATIENTS AND METHODS: 152 pregnancies affected by GDM, without fetal malformations or aneuploidies, were enrolled. Altogether, 746 ultrasound examinations consisting of 7 fetometric parameters each and 1 288 blood glucose daily profiles originating from the 20 (th) to 40 (th) gestational week were systematically investigated for interrelation by correlation and multiple regression analysis. RESULTS: No robust, constant correlation between the analysed parameters could be observed. However, marked differences between latency periods were noticed. Blood glucose parameters, which revealed significant regressions with fetal abdominal circumference, had an average time lag of 6.2 +/- 2.5 weeks, whereas the latency period for head circumference averaged 2.4 +/- 1.2 weeks. The overall small-for-gestational-age (SGA) rate was 20 %, pregnant women with a body mass index > 30 kg / m (2) revealed the highest rate of 28 %. CONCLUSIONS: Therapeutic intervention depending on sonographically detected hypertrophy must be considered as being delayed. The currently valid therapeutic criteria including intended normoglycemia and regular fetometric ultrasound controls cannot prevent markedly high SGA rates, especially among obese women, in adequately treated GDM.

[Pregnancies without prenatal care--which women are potentially affected, what are the inherent fetal risks?]. / Schwangerschaften ohne Vorsorgeuntersuchung--welche Frauen sind potenziell betroffen, welche Risiken ergeben sich für das Kind?

BACKGROUND: In the past decades prenatal care has lead to a reduction in maternal and fetal-neonatal morbidity and mortality. However, the number of examinations that should be recommended - especially in low-risk pregnancies - is still unclear. OBJECTIVE: Women not taking part in prenatal care resemble a subgroup of pregnant women at risk. The objective of this study was to define characteristic parameters based on patient's history and clinical outcome and which maternal and fetal-neonatal morbidity has to be taken into account. PATIENTS AND METHODS: From 913 255 data sets of the Perinatal Registry Lower Saxony, Germany, between 1987 and 1999 n = 2 208 pregnancies (0.24 %) were documented as 'not taken part in prenatal care', while n = 163 143 pregnancies were identified as having undergone optimal prenatal care according to the recommendations. Both groups were compared regarding pregnancy associated and obstetrical parameters. Data are given as odds ratio (OR) and 95 % confidence interval (CI) for pregnancies without any prenatal care vs. pregnancies with standard prenatal care. RESULTS: History of still birth: OR 1.750 (1.175 - 2.609), p < 0.05; mother single: 7.271 (6.603 - 8.006), p < 0.01; maternal age < 18 yrs: 9.904 (7.771 - 12.624), p < 0.01; maternal age > 40 yrs: 3.781 (2.900 - 4.907), p < 0.01; German vs. other origin: 0.214 (0.196 - 0.234), p < 0.01; preterm birth: 2.667 (2.380 - 2.989), p < 0.01; cesarean section: 0.728 (0.644 - 0.823), p < 0.05; birth weight < 5 %: 2.552 (2.140 - 2.943), p < 0.01; APGAR at 1 min < 3: 5.463 (4.521 - 6.602), p < 0.01; umbilical artery pH < 7.0: 2.941 (1.753 - 4.932), p < 0.01; neonatal intubation: 3.945 (3.244 - 4.797), p > 0.01; still birth: 6.089 (4.731 - 7.838), p < 0.01; death post partum: 4.444 (3.008 - 6.567), p < 0.01. CONCLUSION: Pregnant women not taking part in prenatal care are younger or older, more frequently foreigners, and present characteristics of a lower socioeconomic status. These pregnancies are associated with a very high potential of neonatal morbidity. From a both medical and economic point of view, it appears to be reasonable to specifically look after those women before or during pregnancy.

[Marfan syndrome in pregnancy: presentation of four cases and discussion]. / Das Marfan-Syndrom in der Schwangerschaft: Vorstellung von vier Kasuistiken und Diskussion dieser Koinzidenz.

The coincidence of Marfan syndrome and pregnancy means a high risk for mother and child, as it is associated with cardiovascular and obstetric complications. We report our experience of four pregnancies with the Marfan syndrome. The course of pregnancy, the peripartum management and both the maternal and neonatal outcomes of four pregnant women with the Marfan syndrome, who were treated in our department between 1995 and 2005, were retrospectively analysed. The pregnancies of two women were complicated by premature rupture of membranes (36 (th) gestational week) and premature uterine contractions with cervical incompetence (30 (th) gestational week), respectively. One patient developed class 3 (NYHA) heart failure in the 3 (rd) trimenon. Two out of four women had mild cardiovascular disease and could deliver vaginally. In the other two cases a primary Caesarean section was performed at the 36 (th) week of gestation because of severe cardiovascular morbidity. No patient had a progressive aortic dilatation, dissection or rupture. The neonatal outcome was uneventful in all cases. Three newborns underwent a genetic evaluation for the Marfan syndrome, in two of them mutations in the fibrillin 1 gene were detected. Women with the Marfan syndrome should be counselled pre-conception and observed by an interdisciplinary team during pregnancy. If the aortic root diameter is < 40 mm, without progression in pregnancy, and in the absence of severe valve insufficiency, then pregnancy is in most cases well tolerated and vaginal delivery can be performed.