Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial.

BACKGROUND: The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone. METHODS: RATIO37 was a randomised, open-label, multicentre, pragmatic trial, conducted in low-risk pregnant women, recruited from nine hospitals over six countries. The eligibility criteria were designed to be broad; participants were required to be 18 years or older, with an ultrasound-dated confirmed singleton pregnancy in the first trimester, an alive fetus with no congenital malformations at the routine second-trimester ultrasound, an absence of adverse medical or obstetric history, and the capacity to give informed consent. Women were randomly assigned in a 1:1 ratio (block size 100) using a web-based system to either the concealed group or revealed group. In the revealed group, the cerebroplacental ratio value was known by clinicians, and if below the fifth centile, a planned delivery after 37 weeks was recommended. In the concealed group, women and clinicians were blinded to the cerebroplacental ratio value. All participants underwent ultrasound at 36 + 0 to 37 + 6 weeks of gestation with growth assessment and Doppler evaluation. In both groups, planned delivery was recommended when the estimated fetal weight was below the tenth centile. The primary outcome was perinatal mortality from 24 weeks' gestation to infant discharge. The study is registered at ClinicalTrials.gov (NCT02907242) and is now closed. FINDINGS: Between July 29, 2016, and Aug 3, 2021, we enrolled 11 214 women, of whom 9492 (84·6%) completed the trial and were eligible for analysis (4774 in the concealed group and 4718 in the revealed group). Perinatal mortality occurred in 13 (0·3%) of 4774 pregnancies in the concealed group and 13 (0·3%) of 4718 in the revealed group (OR 1·45 [95% CI 0·76-2·76]; p=0·262). Overall, severe neonatal morbidity occurred in 35 (0·73%) newborns in the concealed group and 18 (0·38%) in the revealed group (OR 0·58 [95% CI 0·40-0·83]; p=0·003). Severe neurological morbidity occurred in 13 (0·27%) newborns in the concealed group and nine (0·19%) in the revealed group (OR 0·56 [95% CI 0·25-1·24]; p=0·153). Severe non-neurological morbidity occurred in 23 (0·48%) newborns in the concealed group and nine (0·19%) in the revealed group (0·58 [95% CI 0·39-0·87]; p=0·009). Maternal adverse events were not collected. INTERPRETATION: Planned delivery at term based on ultrasound fetal growth assessment and cerebroplacental ratio at term was not followed by a reduction of perinatal mortality although significantly reduced severe neonatal morbidity compared with fetal growth assessment alone. FUNDING: La Caixa foundation, Cerebra Foundation for the Brain Injured Child, Agència per la Gestió d'Ajuts Universitaris i de Recerca, and Instituto de Salud Carlos III.

Registration of a pregnant woman in the maternity hospital (optimally at 36th-37th weeks) at the Olomouc University Hospital in 2022.

OBJECTIVE: The aim of the study was to analyse the results of the implementation of the new health service Registration of a pregnant woman in the maternity hospital (optimally at 36th-37th weeks) provided as part of outpatient/ambulatory health care at Olomouc University Hospital (OUH). MATERIALS AND METHODS: A prospective cohort study. In 2022, a total of 2,271 women gave birth in OUH, and 2,010 of them were Registered in the maternity hospital, defined specific risks were identified and a pregnancy termination strategy was established/determined. RESULTS: The health service was provided to 88.5% of women giving birth (2,010/2,271). The age of the mothers was 15-56 years (mean 31.3 years; median 31 years), their body mass index was 13.4-53.1 kg/m2 (mean 24.6 kg/m2; median 23.2 kg/m2). 43.6% of them (877/2,010) were Low-risk pregnancies and 56.4% (1,133/2,010) were Pregnancies with a defined specific risk. The most frequently identified risks were as follows: RhD negative blood group (18.4%), diabetes mellitus (13.9%), history of caesarean section (12.0%), hypertensive disorders (6.5%), small fetus/fetal growth restriction (6.3%), risk the development of hemolytic disease in the fetus and the newborn (2.5%), multiple pregnancy (1.6%), congenital malformation of the fetus (1.3%) and placentation disorders (0.5%). In 63.4% of them (1,275/2,010), the pregnancy termination strategy was determined by spontaneous vaginal delivery, in 18.0% (361/2,010) by pre-induction of vaginal delivery and in 14.2% (285/2,010) by caesarean section. In 4.4% (89/2,010) the health service was not implemented correctly because no strategy was established. CONCLUSION: The implementation of the new health service will make it possible to replace activity (more frequent antenatal care contacts/visits and routine antenatal cardiotocography) with efficiency (risk identification, determination of the optimal strategy for outpatient/ambulatory antenatal care and timing and mode of delivery) and thereby provide better and safer health care (from a medical, organizational, legislative and economic points of view).

Prenatal detection of copy number variants in fetuses with detected congenital devolpmental disordes, from 2015 to 2020 by Multiplex Ligation-Dependent Probe Amplification and microarray analysis.

OBJECTIVE: Analysis of prenatal samples from 2015 to 2020. Comparison detection rates of clinically relevant variants by cytogenetic karyotype analysis and cytogenomic MLPA (Multiplex Ligation-Depent Probe Amplification) and microarray methods (CMA - chromosomal microarray). MATERIAL AND METHOD: 1,029 prenatal samples were analyzed by cytogenetic karyotyping (N = 1,029), cytogenomic methods - MLPA (N = 144) and CMA (N = 111). All unbalanced changes were confirmed by MLPA or CMA. RESULTS: From the analyzed set of fetuses, after subtraction of aneuploidies - 107 (10.40%, N = 1,029), 22 structural aberrations (2.39%, N = 922) - nine unbalanced changes (0.98%), 10 balanced changes (1.08%), one case of unclear mosaicism (0.09%), one case of presence of a marker chromosome (0.09%) and one case of sex discordance (0.09%) - were detected by karyotype analysis. A total of eight (7.21%, N = 111) pathological variants were detected by CMA in 255 samples with physiological karyotype indicated for cytogenomic examination. Five (3.47%, N = 144) of eight pathogenic variants were detected by MLPA method. The total capture of pathogenic variants by MLPA and CMA methods was 14 (5.14%) and 17 (6.25%) (N = 272), including confirmatory pathological karyotype testing. Detection of pathological variants in the isolated disorders group was lower than in the multiple disorders group (5.08 vs. 21.42%). CONCLUSION: A higher success rate for the detection of pathological copy number variation variants by the microarray method than by the MLPA method was confirmed.

Medical Termination of Pregnancy (MToP) in the 1st trimester - the role of human chorionic gonadotropin and ultrasound in pregnancy diagnosis and MToP follow-up.

OBJECTIVE: In the Czech Republic, it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester up until the 49th day of secondary amenorrhea. The aim of the study is to analyse the significance of serum/urine human chorionic gonadotropin (hCG) assessment and ultrasound (US) examination in pregnancy diagnosis and MToP follow-up. METHODS: In 2017-2018, MToP was carried out in a total of 109 women by administering a combination of mifepristone (600 mg orally) and misoprostol (400 mcg orally). Serum/urine (LSUP - low sensitivity urine pregnancy test) hCG assessment and US examination were performed at pregnancy diagnosis and MToP follow-up. RESULTS: At pregnancy diagnosis, there was a positive and medium strong correlation between serum hCG and size of the gestational sac - GS (R = 0.711; P  1,000 IU/L and LSUP test was always positive). In 5.5% of women (6/109), a subsequent surgical intervention was carried out including those with ongoing pregnancy (N = 5); missed abortion (N = 1) was treated by additional misoprostol, where surgical intervention was not necessary. CONCLUSION: At pregnancy diagnosis, there is a positive and medium strong correlation between serum hCG and CRL. In MToP follow-up, a negative LSUP test enables reliable exclusion of ongoing pregnancy and missed abortion. In case of a positive LSUP test, US examination should be performed; however, surgical intervention should not be indicated solely on the basis of uterine cavity dilatation.

Prospective comparison of cervical ripening with double balloon Cook catheter, misoprostol or dinoprostone in term singleton pregnancies.

OBJECTIVES: Induction of labor is indicated if the risk of continuing pregnancy is higher (either for fetus or mother) than the risk associated with the induction itself. The purpose of the present study was to compare the effectiveness of the double balloon Cook catheter and pharmacological preparations - prostaglandins (PGE), in our case it was misoprostol (PGE1) or dinoprostone (PGE2) for cervical ripening in pregnant women with gestational age at term. MATERIAL AND METHODS: The prospective observational study was conducted from March 2017 to December 2018. We used mechanical and pharmacological methods for cervical ripening. We compared the efficiency of methods and time to delivery from start of cervical ripening. We also evaluated the neonatal complications by Apgar score and neonatal intensive care unit admission in three different groups. RESULTS: Two hundred and nine women were chosen for cervical ripening. Double balloon Cook catheter and misoprostol were equally efficient in achieving vaginal delivery (76%). The shortest time for cervical ripening and successful vaginal delivery was shown in misoprostol (PGE1) group. In conclusion, no significant differences were found between groups in all neonatal outcomes. CONCLUSIONS: Currently, many methods of delivery preinduction exist and the prevalence of their usage varies considerably between countries. As yet, there is no literature comparing these three methods for the preparation of cervix.

Screening for congenital defects and genetic diseases of the fetus at University Hospital in Olomouc and sending/ reporting to the National register of reproductive health in the Czech Republic.

OBJECTIVE: The aim of the study was to analyze the results of the screening for congenital defects (CD) and genetic diseases (GD) of the fetus in the Fetal Medicine Centre at the Department of Obstetrics and Gynecology, University Hospital in Olomouc. MATERIALS AND METHODS: Prospective cohort study. In the period from 1 January 2020 to 31 December 2021, a total of 14,460 health services were performed on 4,916 pregnant women. Within the screening of CD and GD of the fetus, 501 pregnant women were found to have an abnormality requiring further clinical management, 170 of them were diagnosed with a CD of the fetus and in 20 cases a GD of the fetus was diagnosed by a laboratory genetic examination. All diagnosed fetal CD and GD were sent/ reported according to the valid methodology of the National health information system (NHIS) to the National register of reproductive health (NRRH) to the CD Module. RESULTS: An increased calculated individual risk of genetic fetal disease was diagnosed in the first trimester of pregnancy in 10.7% of fetuses (319/ 2,968), and in the second trimester in 0.9% of fetuses (27/ 2,948). Nuchal translucency (NT) > 3.5 mm was diagnosed in 0.9% of fetuses by ultrasound examination in the first trimester of pregnancy (26/ 2,968). In fetal CD and GD screening, 501 pregnant women were found to have an abnormality requiring further clinical management, 72.1% of women (361/ 501) had an increased risk of genetic fetal disease, and diagnostic examination of the fetal genetic material obtained by invasive procedure (chorionic villus sampling or amniocentesis) was indicated. A total of 31.3% of them (113/ 361) refused the invasive procedure and 2.5% (9/ 361) did not attend the planned procedure; the invasive procedure was performed in 66.2% (239/ 361). CONCLUSION: Comparing the results of CD and GD fetal screening in our medical facility with other specialized medical facilities in the Czech Republic is currently difficult to do, but information from the NRRH could allow objective and transparent comparisons in the future.

Abortion: legislation and statistics in Europe.

Objective: The Parliamentary Assembly invited the member states of the Council of Europe to 'guarantee women's effective exercise of their right of access to a safe and legal abortion'. While abortion legislation and statistics give an impression of the legislative, cultural, and religious views of the societies and the socio-economic health of the female population, only one study conducted in 2011 looked into the current legislation and trends in terminations of pregnancy in the European Union.Materials and Methods: From January 2017 to December 2018, a group of experts, the authors of the present article, liaised with colleagues practising in 32 European countries to collect data on abortion legislation and statistics using three different questionnaires.Results: The article presents the results of this initiative and compares the status quo and recent trends in abortion legislation and statistics across Europe.Conclusions: The European legislations are still very heterogenous and abortion rates vary widely between countries, confirming that laws do not correlate with abortion rates. This compilation of data, also available on a website (www.abort-report.eu), may help to change laws to better meet the needs of women who decided to have an abortion as a solution to the underlying problem of an unwanted pregnancy.

Should 3D volume assessment of the corpus callosum and cerebellar vermis be a part of a routine second trimester screening?

BACKGROUND: The majority of fetal structural defects can be detected in the second trimester, thus this is the main time for screening for structural defects. 3D imaging of the fetal brain does not create a common part of this screening. METHODS: This prospective observational study was conducted at the Fetal Medicine Center of The Gynecological-Obstetrical Department of the University Hospital Olomouc in years 2017-2020. The study sample was 451 consecutively scanned morphologically normal fetuses attending for routine second trimester anatomical survey at 20-22 weeks of pregnancy. A transabdominal 3D ultrasound volume acquisition of fetal brain was obtained from an axial and sagittal plane using skull sutures as an acoustic window. RESULTS: Both the corpus callosum (CC) and the vermis (VC) were detected in 51.7% of examinations in the sagittal plane, and in 31.7% in the axial plane. In 61.9% of the examinations, there was at least partial detection in both planes. Maternal BMI was found to be the only significant predictor of the quality of imaging in both planes. CONCLUSION: 3D acquisition of fetal brain images in the sagittal plane followed by manipulation of acquired volume was valuable in assessment of corpus callosum and cerebellar vermis. This allows reconstruction of the sagittal plane that can be difficult to obtain in 2D imaging.

Effect of Maternal and Fetal Characteristics in Feto-Placental Doppler and Impact of Using Adjusted Standards in the Definition of Fetal Growth Restriction at Term.

INTRODUCTION: This study aimed to determine the effect and clinical impact of physiological characteristics on the 95th/5th centile of the umbilical artery (UA) Doppler and the cerebroplacental ratio (CPR), at 36+ weeks. METHODS: From the multicenter randomized trial "Ratio37," we selected 4,505 low-risk pregnant women between June 2016 and January 2020. We registered physiological characteristics and the pulsatility indexes (PI) of the UA and middle cerebral artery (36-39 weeks). The 95th/5th centile of the UA PI and CPR was modeled by quantile regression. To evaluate the clinical impact of adjusting Doppler, we retrospectively applied gestational age (GA) and fully adjusted standards to 682 small for gestational age (SGA)-suspected fetuses (37 weeks) from a cohort of consecutive patients obtained between January 2010 and January 2020. RESULTS: Several physiological characteristics significantly influenced the 95th/5th centile of the UA and CPR PI. The fully adjusted 95th centile of the UA was higher, and the 5th centile of the CPR was lower than GA-only-adjusted standards. Of the 682 SGA fetuses, 150 (22%) were classified as late fetal growth restricted only by GA and 112 (16.4%) when we adjusted Doppler. These 38 fetuses had similar perinatal outcome than the SGA group. DISCUSSION: The 95th/5th centile of the UA and CPR PI is significantly influenced by physiological characteristics. Adjusting Doppler standards could differentiate better between FGR and SGA.

Comparison of dinoprostone, misoprostol and amniotomy in labor induction.

OBJECTIVE: Comparison of dinoprostone, misoprostol and amniotomy in labor induction. METHODS: The study group included a total of 437 women who underwent consecutive induction of labor after evaluation of the indication and Bishops score. The most common indications were: postmaturity, hypertensive disease, diabetes mellitus and fetal growth restriction. In 327 cases we chose to induce labor using vaginal tablets of dinoprostone at a dose of 0.75mg, in 36 cases dinoprostone at a dose of 3mg, in 16 cases we used a vaginal insert of misoprostol (200 µg), and in 58 cases amniotomy was performed. RESULTS: In the subgroup of dinoprostone (0.75mg) the rate of vaginal delivery (including extraction delivery) was 90.2%, in the subgroup of dinoprostone (3mg) it was 91.6%, in the subgroup of misoprostol it was 100% and in the subgroup of amniotomy it was 93.1%. The time period between onset of labor induction and delivery was an average of 15.75 hours in the dinoprostone (0.75mg) subgroup, 21.41 hours in the dinoprostone (3mg) subgroup, 17.41 hours in the misoprostol subgroup and 7.49 hours in the amniotomy subgroup. CONCLUSION: Subgroup of patients with misoprostol showed the highest rate of vaginal delivery after labor induction. In the subgroup with amniotomy, the shortest time period between onset of induction and delivery was reached.

Two Reliable Methodical Approaches for Non-Invasive RHD Genotyping of a Fetus from Maternal Plasma.

Noninvasive fetal RHD genotyping is an important tool for predicting RhD incompatibility between a pregnant woman and a fetus. This study aimed to assess a methodological approach other than the commonly used one for noninvasive fetal RHD genotyping on a representative set of RhD-negative pregnant women. The methodology must be accurate, reliable, and broadly available for implementation into routine clinical practice. A total of 337 RhD-negative pregnant women from the Czech Republic region were tested in this study. The fetal RHD genotype was assessed using two methods: real-time PCR and endpoint quantitative fluorescent (QF) PCR. We used exon-7-specific primers from the RHD gene, along with internal controls. Plasma samples were analyzed and measured in four/two parallel reactions to determine the accuracy of the RHD genotyping. The RHD genotype was verified using DNA analysis from a newborn buccal swab. Both methods showed an excellent ability to predict the RHD genotype. Real-time PCR achieved its greatest accuracy of 98.6% (97.1% sensitivity and 100% specificity (95% CI)) if all four PCRs were positive/negative. The QF PCR method also achieved its greatest accuracy of 99.4% (100% sensitivity and 98.6% specificity (95% CI)) if all the measurements were positive/negative. Both real-time PCR and QF PCR were reliable methods for precisely assessing the fetal RHD allele from the plasma of RhD-negative pregnant women.

Prescriptive Reference Standards of Third-Trimester Cerebroplacental Ratio and Its Physiological Determinants.

OBJECTIVE: To construct valid reference standards reflecting optimal cerebroplacental ratio and to explore its physiological determinants. METHODS: A cohort of 391 low-risk pregnancies of singleton pregnancies of nonmalformed fetuses without maternal medical conditions and with normal perinatal outcomes was created. Doppler measurements of the middle cerebral artery and umbilical artery were performed at 24-42 weeks. Reference standards were produced, and the influence of physiological determinants was explored by nonparametric quantile regression. The derived standards were validated in a cohort of 200 low-risk pregnancies. RESULTS: Maternal body mass index was significantly associated with the 5th centile of the cerebroplacental ratio. For each additional unit of body mass index, the 5th centile was on average 0.014 lower. The derived 5th, 10th, and 50th centiles selected in the validation cohort were 5, 9.5, and 51% of the measurements. CONCLUSIONS: This study provides methodologically sound prescriptive standards and suggests that maternal body mass index is a determinant of a cutoff commonly used for decision-making.

Management of very early medical abortion-An international survey among providers.

OBJECTIVE: To record the definition and management of Very Early Medical Abortion (VEMA) in different countries. STUDY DESIGN: An Internet survey was circulated internationally among providers of medical abortion via a website. The questionnaire focused on reasons for performing or delaying medical abortion at a very early gestational age and the perceived advantages and disadvantages of VEMA. RESULTS: Out of 220 completed questionnaires, 50 % came from European abortion providers (n = 110). Most respondents (72 %) defined VEMA as abortion performed in the presence of a positive hCG pregnancy test but with an empty uterine cavity or a gestational sac-like structure, and no signs or symptoms of ectopic pregnancy. A total of 74 % of respondents thought it was not necessary to wait for a diagnosis of intrauterine pregnancy before starting medical abortion. Equally, 74 % were aware of the possibility of an ectopic pregnancy. CONCLUSION: According to European providers of medical abortion, waiting for the diagnosis of an intrauterine pregnancy is not necessary and does not improve treatment of ectopic pregnancy. Providers should know that medical abortion can be performed effectively and safely as soon as the woman has decided. There is no lower gestational age limit.

Outcome of first trimester medical termination of pregnancy: definitions and management.

OBJECTIVE: Medical termination of pregnancy (MToP, or medical abortion) is a highly effective method with a reported efficacy of 95-98%. However, different criteria are currently used to define success, and there are different recommendations for the treatment of what is considered a failure of MToP. This work was undertaken to develop a consensus around a set of well-defined MToP outcomes, as recommended by the Core Outcomes in Women's and Newborn Health initiative. METHODS: A literature search was made of national and international guidelines and of recommendations of expert groups for various outcomes of MToP and subsequent management. Based on a review of the findings, a group of European experts in MToP undertook a consensus process to agree on a set of core MToP outcomes. RESULTS: The following core MToP outcomes were defined: success, failure (ongoing pregnancy), need for additional treatment (medical or surgical) to complete MToP (missed abortion, incomplete abortion), complications and the woman's request for additional treatment (medical or surgical). Recommendations for the management of unsuccessful outcomes were also formulated. CONCLUSION: New definitions of MToP outcomes that are more focused on objective criteria and consequently less dependent on provider interpretation are proposed. This should allow better comparison of the efficacy of different regimens and improve the management of failed or incomplete abortion.

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol.

INTRODUCTION: Fetal growth restriction (FGR) affects 5%-10% of all pregnancies, contributing to 30%-50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. METHODS AND ANALYSIS: The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19+0-22+6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36+0-37+6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36+0-37+6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT02907242; pre-results.

High incidence of monozygotic twinning in infertility treatment.

BACKGROUND: Monozygotic twinning is associated with increased perinatal morbidity and mortality. There is evidence that the number of monozygotic twins increases after assisted reproductive techniques. METHODS: We searched PUBMED, MEDLINE, and Scopus from 1987 to 2015 for studies analyzing the incidence and possible etiology of monozygotic twinning in infertility patients and critically reviewed the current state of knowledge. RESULTS AND CONCLUSIONS: Monozygotic twinning is a rare in natural conception but occurs around twice the normal rate after assisted reproduction. Factors associated with this phenomenon remain speculative, though there is some evidence that micromanipulation techniques, prolonged culture, and genetics are involved. In view of the possible complications, adequate pre-conception counselling is advocated.

Clinical Potential of Effective Noninvasive Exclusion of KEL1-Positive Fetuses in KEL1-Negative Pregnant Women.

BACKGROUND: The clinical importance of assessing the fetal KEL genotype is to exclude 'K'-positive fetuses (genotype KEL1/KEL2) in 'K'-alloimmunized pregnant women (genotype KEL2/KEL2). Noninvasive assessment of the fetal KEL genotype is not yet available in the Czech Republic. OBJECTIVE: The aim of this study was to assess the fetal KEL1/KEL2 genotype from cell-free fetal DNA in the plasma of KEL2/KEL2 pregnant women. METHODS: The fetal genotype was assessed by minisequencing (a dilution series including control samples). A total of 138 pregnant women (between the 8th and 23rd gestational week) were tested by minisequencing. The fetal genotype was further verified by analysis of a buccal swab from the newborn. RESULTS: Minisequencing proved to be a reliable method. In 2.2% (3/138) of the examined women, plasma sample testing failed; 94.8% (128/135) had the KEL2/KEL2 genotype, and a total of 3.1% of fetuses (4/128) had the KEL1/KEL2 genotype. Sensitivity and specificity reached 100% (p < 0.0001). CONCLUSION: Minisequencing is a reliable method for the assessment of the fetal KEL1 allele from the plasma of KEL2/KEL2 pregnant women.

Markers of endothelial activation in preeclampsia.

BACKGROUND: The study aimed at finding a laboratory approach to detect endothelial damage in normal pregnancy as well as in pregnancy complicated by preeclampsia using selected markers of endothelial activation. MATERIALS: A total of 403 healthy pregnant women without a history of deep vein thrombosis and/or hypertension were prospectively studied. From all women, venous blood was collected before the end of the 1st trimester, between weeks 24 and 28 of gestation, and in the 3rd trimester (weeks 34-36). Assays of tissue plasminogen activator, plasminogen activator inhibitor-1, von Willebrand factor activity and antigen, thrombomodulin, endothelial protein C receptor, and endothelial microparticles activated by TF were performed. RESULTS: When comparing women who developed preeclampsia during pregnancy (the average levels were 23.41 µg/L, 34.33 µg/L, and 53.56 µg/L in the 1st, 2nd, and 3rd trimesters, respectively) with healthy pregnant women (the average levels were 19.05 µg/L, 28.47 µg/L, and 39.86 µg/L in the 1st, 2nd, and 3rd trimesters, respectively) significant differences in the levels of thrombomodulin were found in all three trimesters. By contrast, no statistically significant differences in the levels of vWF (both antigen and activity), t-PA, EPCR, EMPs, MMP-2, MMP-9, and TIMP-9 were found in any trimesters in the same group. CONCLUSIONS: Pregnancy and preeclampsia strongly influence the levels of studied markers. The findings of this work confirm the possible predictive potential of thrombomodulin and PA-1.

Changes in middle cerebral artery velocimetry of fetuses diagnosed postnatally with mild or moderate hemolytic disease.

OBJECTIVES: To determine the longitudinal trends of middle cerebral artery peak systolic velocity (MCA PSV) in fetuses with mild or moderate hemolytic disease according to the need for postnatal therapy. DESIGN: Prospective cohort study. SETTING: University referral center. SAMPLE: Twenty-three fetuses from singleton alloimmunized pregnancies. METHODS: Serial measurements of MCA PSV were performed. After delivery, newborns were grouped by the need for postnatal management into mild hemolytic disease, which required no or only phototherapy (n = 14, group 1), and moderate hemolytic disease, where postnatal top-up or exchange transfusions were required (n = 9, group 2). MAIN OUTCOME MEASURES: Serial Doppler MCA PSV data transformed to multiples of the median, analyzed with linear regression and exponential models. RESULTS: We performed 83 measurements in group 1: 3-8 per fetus; mean GA at inclusion, 23 weeks and 65 measurements in group 2: 4-15 per fetus; mean GA at inclusion, 22 weeks. The estimated mean slopes of the MCA PSVs increased with the degree of postnatal therapy required (group 1: MCA PSV = 0.003 GA + 1.298; group 2: MCA PSV = 0.035 GA + 0.436). The relative average increments (RAI) were 4.7% and 7.1%, respectively. The two groups exhibited significant differences in mean slope and RAI (p<0.05). CONCLUSIONS: Fetuses that required postnatal transfusions due to hemolytic disease showed an enhanced progressive increase in MCA PSVs compared to those without transfusion requirement. This information might enable their identification during pregnancy.

Ultrasound evaluation of fetal gender at 12-14 weeks.

AIMS: The aim of this study was to assess the feasibility and accuracy of fetal gender assignment by transabdominal ultrasound at 12-14 weeks of gestation. METHODS: Fetal gender assessment was performed in 1222 singleton pregnancies. In all fetuses the crown-rump length (CRL) was measured and the genital area of the fetus was examined in the mid-sagittal plane. The result of ultrasound examination was compared to the phenotypic sex of the newborn after delivery. RESULTS: The feasibility as well as accuracy in determining gender increased with growing fetal CRL. At CRL < 50 mm (gestational age < 11+4) the feasibility was 39.1% and accuracy 30.5% (40.9% in male gender vs 24.3% in female gender). At CRL 50-54.9 mm (gestational age 11+4 to 12+0) the feasibility was 63.5% and accuracy 75.0% (89.1% in male gender vs 66.7% in female gender). At CRL 55-59.9 mm (gestational age 12+0 to 12+2) the feasibility was 90.5% and accuracy 96.6% (99.1% in male gender vs 93.5% in female gender). At CRL ≥ 60 mm (gestational age ≥ 12+2) the feasibility was 97.4% and accuracy 100.0% (100.0% in male gender vs 100.0% in female gender). CONCLUSIONS: Fetal gender may reliably be determined when CRL ≥ 60 mm (gestational age ≥ 12+2). Male gender may already be reliably determined when CRL ≥ 55 mm (gestational age ≥ 12+0). If CRL < 50 mm (gestational age < 11+4) the gender cannot be reliably predicted.