Showing papers in "Fetal Diagnosis and Therapy in 2012"
TL;DR: Low-dose aspirin administrated at or before 16 weeks of gestation reduces the risk of preterm but not term preeclampsia, according to a systematic review and meta-analysis of randomized controlled trials.
Abstract: Objective: To compare the effect of early administration of aspirin on the risk of preterm and term preeclampsia. Method: A systematic review and meta-analysis of randomized controlled trials were performed. Women who were randomized to low-dose aspirin or placebo/no treatment at or before 16 weeks of gestation were included. The outcomes of interest were preterm preeclampsia (delivery Results: The search identified 7,941 citations but only five trials on a combined total of 556 women fulfilled the inclusion criteria. When compared to controls, aspirin initiated ≤16 weeks of gestation was associated with a major reduction of the risk of preterm preeclampsia (RR 0.11, 95% CI 0.04–0.33) but had no significant effect on term preeclampsia (RR 0.98, 95% CI 0.42–2.33). Conclusion: Low-dose aspirin administrated at or before 16 weeks of gestation reduces the risk of preterm but not term preeclampsia.
339 citations
TL;DR: A new model has been developed for effective first-trimester screening for PE based on maternal characteristics and biophysical markers at 11–13 weeks’ gestation in which gestation at the time of delivery for PE is treated as a continuous variable.
Abstract: Objective: It was the aim of this study to develop models for the prediction of preeclampsia (PE) based on maternal characteristics and biophysical markers at 11–
184 citations
TL;DR: Performance of screening for PE by taking the average of a minimum of two measurements from both arms is comparable to the NHFA protocol.
Abstract: Objectives: To identify the best protocol for measurement of mean arterial pressure (MAP) in early pregnancy for the prediction of preeclampsia (PE). Methods: This was a prospective study in singleton pregnancies attending for a routine hospital visit at 11-13 weeks' gestation when a minimum of four recordings of MAP were taken from each arm. The performance of screening for PE by different combinations of MAP was compared to the protocol of the National Heart Foundation of Australia (NHFA). Results: The MAP was measured in 587 (2.4%) cases that developed PE and in 22,900 that were unaffected by hypertensive disorders in pregnancy. The area under the receiver operating characteristic curve (AUROC) for prediction of PE by MAP as recommended by the NHFA protocol was 0.773 (95% CI 0.768-0.778). This AUROC was not significantly different from the AUROC obtained by the average MAP of the first three measurements from one arm (0.765, 95% CI 0.760-0.771) or the average of the first (0.766, 95% CI 0.760-0.771), the first two (0.771, 95% CI 0.766-0.777), or the first three measurements from the two arms (0.773, 95% CI 0.768-0.778). Conclusion: Performance of screening for PE by taking the average of a minimum of two measurements from both arms is comparable to the NHFA protocol.
183 citations
TL;DR: The fetal fraction in maternal plasma cfDNA increases with serum PAPP-A and free β-hCG and decreases with maternal weight, but not by other maternal characteristics, fetal karyotype, crown-rump length or nuchal translucency thickness.
Abstract: Objective: It was the aim of this study to examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free DNA (cfDNA) at 11–13 weeks’ gestation. Methods: In a nested case-control study, cfDNA was extracted from maternal plasma obtained before chorionic villous sampling from 300 euploid, 50 trisomy 21 and 50 trisomy 18 pregnancies at 11–13 weeks’ gestation. Chromosome-selective sequencing of maternal cfDNA nonpolymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of DNA which is of fetal origin. Multivariate regression analysis was used to determine which of the factors amongst maternal weight, racial origin, smoking status, plasma storage time, serum pregnancy-associated plasma protein (PAPP)-A and free -subunit of human chorionic gonadotropin ( hCG), fetal crown-rump length, nuchal translucency thickness, gender and karyotype were significant predictors of the fetal fraction. Results: Significant independent prediction of fetal fraction was provided by maternal weight, se
166 citations
TL;DR: The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function and is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome.
Abstract: Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55-60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome.
128 citations
TL;DR: Technical issues and limitations in fetal cardiac function evaluation are summarized, as well as its potential research and clinical applications, which suggest functional fetal echocardiography is a promising tool that may soon be incorporated into clinical practice.
Abstract: Fetal echocardiography was initially used to detect structural anomalies but has more recently also been proposed to assess fetal cardiac function. This review summarizes technical issues and limitations in fetal cardiac function evaluation, as well as its potential research and clinical applications. Functional echocardiography has been demonstrated to select high-risk populations and to be associated with outcome in several fetal conditions including intrauterine growth restriction, twin-to-twin transfusion syndrome, maternal diabetes, and congenital diaphragmatic hernia. Fetal heart evaluation is challenging due to the smallness and high heart rate of the fetus and restricted access to the fetus far from the transducer. Due to these limitations and differences in cardiac function which are related to fetal maturation, cardiovascular parameters should be validated in the fetus and used with caution. Despite these precautions, in expert hands and with appropriate ultrasound equipment, evaluation of cardiac function is feasible in most fetuses. Functional fetal echocardiography is a promising tool that may soon be incorporated into clinical practice. Research is warranted to further refine the contribution of fetal cardiac assessment to the diagnosis, monitoring, or prediction of outcomes in various fetal conditions.
124 citations
TL;DR: The maximum diameter of the instrument explains iPPROM rate, gestational age at birth and fetal survival as well as fetal survival after representative minimally invasive antenatal procedures.
Abstract: Objective: Iatrogenic preterm prelabor rupture of membranes (iPPROM; Methods: We systematically reviewed reported iPPROM rates, gestational age at delivery and fetal survival after representative minimally invasive antenatal procedures. Results: A total of 1,146, 36 and 194 cases with mean iPPROM rates of 27, 31 and 26% were included for placental laser in twin-twin transfusion syndrome, shunting in lower urinary tract obstruction and interventions for twin-reversed arterial perfusion, respectively. In the statistical analysis, the maximum diameter of the instrument predicted iPPROM rate and was significantly related to gestational age at birth as well as fetal survival. Information on duration of the respective procedures was scarce and did not allow for meaningful analysis. Conclusions: iPPROM occurs in about 30% of cases treated by minimally invasive fetal surgery. The maximum diameter of the instrument explains iPPROM rate, gestational age at birth and fetal survival. Great variations in the reporting of iPPROM make data analysis difficult.
120 citations
TL;DR: In this paper, the authors established a normal range of birthweight with gestational age at delivery and examined the contribution of maternal characteristics in defining growth restriction in stillbirths and found that there was a polynomial association between birthweight and GA.
Abstract: Objective: To establish a normal range of birthweight with gestational age (GA) at delivery and examine the contribution of maternal characteristics in defining growth restriction in stillbirths. Methods: In 69,895 normal singleton pregnancies, regression analysis was used to determine the association of birthweight with GA and maternal characteristics. The proportion of 290 stillbirths classified as small for GA depending on inclusion or exclusion of maternal characteristics was determined. Results: In normal pregnancies, there was a polynomial association between birthweight and GA. Birthweight increased with maternal weight, height and parity and was lower in Africans and South Asians than in Caucasians. Birthweight for GA was reduced in antepartum stillbirths (n = 243; p ! 0.0001) but not in intrapartum stillbirths (n = 47; p = 0.334). There was no significant difference in the proportion of antepartum stillbirths with birthweight below the 10th percentile when birthweight was corrected for GA only compared to correction for GA and maternal characteristics (53.1 vs. 54.3%). The birthweight was
116 citations
TL;DR: Effective first-trimester screening for spontaneous early preterm delivery can be provided by a combination of maternal characteristics and cervical length.
Abstract: Objective: It was the aim of this study to examine the potential value of cervical length at 11–13 weeks’ gestation in the prediction of spontaneous preterm deliv
97 citations
TL;DR: Normative references of left modified MPI from 11 to 41 weeks of gestation are provided, which could be useful in the assessment of cardiac function in fetuses.
Abstract: Objective: To establish normal reference intervals of the fetal left modified myocardial performance index (MPI) with the use of stringent criteria for delimitati
85 citations
TL;DR: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation, and decision tree analysis identified gestational age at birth as the best predictor of death.
Abstract: Objective: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intr
TL;DR: A standard protocol with fixed acquisition and processing settings, including manual indication of the timing events of the cardiac cycle to correct for the lack of ECG, was feasible and reproducible for the evaluation of longitudinal ventricular strain and strain rate of the fetal heart by TDI as well as 2D-strain analysis.
Abstract: Purpose: Assessment of cardiac function in the fetal heart is challenging because of its small size and high heart rate, restricted physical access to the fetus,
TL;DR: A simplified approach to the understanding of MC twin pregnancy, its potential complications, and the key concepts allowing adequate differential diagnosis and targeted management is proposed.
Abstract: Monochorionic (MC) twins represent a significant proportion of perinatal morbidity and mortality. Overall, 1 of 3 MC twin pregnancies will develop complications in relation to the MC placenta and the presence of interfetal placental anastomoses. From a clinical standpoint, these complications can be grouped into four main types of clinical problems: chronic transfusion, acute transfusion, growth discordance, and discordant malformation. Differential diagnosis of MC twin complications is still challenging due to frequent overlap of their clinical signs and the complex relationships between them. Clinical experience demonstrates that most instances of wrong management derive from failure to comply with a basic set of rules for diagnosis and management. In this review, we propose a simplified approach to the understanding of MC twin pregnancy, its potential complications, and the key concepts allowing adequate differential diagnosis and targeted management.
TL;DR: The combination of insight into the measurement techniques and their limitations, together with knowledge of myocardial mechanics and physiology, opens new perspectives to improve the assessment and management of fetal, pediatric, and adult patients.
Abstract: The assessment of cardiac pump function and the potential of local myocardium to contribute to the overall performance are of great importance in many cardiovascular abnormalities. Assessing intrinsic cardiac function requires obtaining information on the true contractility of the heart muscle, assessed locally but interpreted in the context of its contribution to the global ejection performance and potential to adapt to changing circumstances. Contemporary imaging techniques offer the possibility of noninvasive quantification of myocardial deformation. These new clinical tools are attractive to use for the assessment of ventricular function. However, it is of great importance to understand cardiac mechanics - a complex interplay between the tissue structure/shape, force development, and interaction with the environment/neighbors - to interpret alterations in deformation and to extract clinically relevant conclusions. The combination of insight into the measurement techniques and their limitations, together with knowledge of myocardial mechanics and physiology, opens new perspectives to improve the assessment and management of fetal, pediatric, and adult patients.
TL;DR: BCT tubes are suitable for shipping whole blood prior to processing with respect to cell-free DNA levels, and will benefit the development and clinical application of noninvasive methods of fetal diagnosis that utilize cf-DNA.
Abstract: Objective: To determine the effect of shipping blood in Streck blood collection tubes (BCT) prior to processing on cell-free DNA (cf-DNA) levels. Methods: Blood was collected in ethylenediaminetetraacetic acid (EDTA) and BCT tubes from 10 pregnant women carrying male fetuses. One set of each tube for each subject was processed to plasma immediately (standard cf-DNA protocol), whereas the other set was shipped by air courier and then processed. DNA was extracted and total and fetal DNA concentrations were measured by TaqMan multiplexed quantitative real-time PCR. Results: No significant difference was observed in total cf-DNA in plasma between immediately processed EDTA (control) and immediately processed BCT samples. Moreover, no significant change in total cf-DNA was detected in plasma of BCT samples shipped at room temperature. Significant differences in total cf-DNA leading to a significantly decreased fetal fraction were found in shipped EDTA samples and BCT samples shipped at 4°C. Discussion: BCT tubes are suitable for shipping whole blood prior to processing with respect to cf-DNA levels. However, care should be taken to ensure that samples are not exposed to extreme temperatures during shipment. This finding will benefit the development and clinical application of noninvasive methods of fetal diagnosis that utilize cf-DNA.
TL;DR: In the fetus, most current methods of acquisition result in frame rates that are too low, and the fetal heart size is too small to achieve reliable measures of fetal myocardial deformation.
Abstract: Objective: To report the current status of speckle tracking techniques in evaluation of fetal myocardial deformation. Methods: A variety of non-Doppler ultrasound methods are available using offline analysis of standard four-chamber and short axis views of the heart. Results: Most reports have used techniques developed for the measurement of strain and strain rate in the adult heart and produced conflicting descriptions of gestational changes in strain. Myocardial velocities usually reflect mean modal velocities and are lower than the peak velocities obtained using Doppler techniques. Conclusions: In the fetus, most current methods of acquisition result in frame rates that are too low, and the fetal heart size is too small to achieve reliable measures of fetal myocardial deformation.
TL;DR: Tissue Doppler echocardiography is being increasingly used in fetal medicine as a clinical and research tool and TDI is a sensitive and promising method to evaluate fetal cardiac function.
Abstract: Objective: Tissue Doppler echocardiography is being increasingly used in fetal medicine as a clinical and research tool. The objective of this study was to review the current status of tissue Doppler imaging (TDI) techniques applied to the fetus. Methods: Fetal cardiac function was evaluated using spectral and color TDI modes in normal fetuses and in several clinical conditions. Results: Annular peak velocities and their ratios as well as the myocardial performance index were evaluated using spectral TDI, and changes throughout gestation were described. Color TDI has several limitations in fetal life, particularly the use of low frame rates with current methods of acquisition and the lack of normal references for deformation parameters. Conclusions: Despite its limitations, TDI is a sensitive and promising method to evaluate fetal cardiac function.
TL;DR: Inclusion of serum PLGF improves the performance of the first-trimester combined test in screening for trisomy-21, and reduces the false positive rate and increases the detection rate.
Abstract: Objective: To investigate whether measurement of maternal serum placental growth factor (PLGF) can improve the performance of first-trimester combined screening for trisomy-21 by fetal nuchal translucency (NT) thickness and serum free -human chorionic gonadotropin ( -hCG) and PAPP-A Methods: In singleton pregnancies attending for routine care, serum PLGF, free -hCG and PAPP-A were measured at 8 +0 –13 +6 weeks’ gestation, and fetal NT was measured at 11 +0 –13 +6 weeks The population included 12,154 normal and 44 trisomy-21 pregnancies We examined the effect of adding PLGF on the performance of screening by the combined test Results: In the trisomy-21 pregnancies the median multiple of the normal median PLGF, adjusted for gestational age, maternal weight, racial origin, smoking status and method of conception, was significantly reduced (06070, 95% CI 05543–06648), and this did not change significantly
TL;DR: In the assessment of GO fetuses, MRI-based O/E TLV of <50% was predictive of increased postnatal morbidity and lower Apgar scores at birth compared to patients with ≥50% of expected O/e TLV.
Abstract: Objective To determine the value of fetal MRI-calculated total lung volumes (TLV) in the prediction of short-term outcome in patients with giant omphalocele (GO). Material and methods We reviewed all cases of GO undergoing fetal MRI after 21 weeks' gestation and receiving postnatal care at our institution between 2003 and 2010. Observed/expected (O/E) TLV was calculated using age-matched TLV normograms [Radiology 2001;219:236-241]. Postnatal outcomes were stratified based on O/E TLV above or below 50% of expected. Results Seventeen GO cases fulfilled the entry criteria. The mean age at fetal MRI evaluation was 25.8 ± 4.8 weeks' gestation. The mean GO TLV (21.0 ± 13.2) was lower than age-matched population norms (p Conclusion In the assessment of GO fetuses, MRI-based O/E TLV of
TL;DR: The extent to which a fetus is influenced by the maternal anesthesia depends on the type of anesthesia, with different needs for extra fetal anesthesia or analgesia.
Abstract: For many prenatally diagnosed conditions, treatment is possible before birth. These fetal procedures can range from minimal invasive punctions to full open fetal surgery. Providing anesthesia for these procedures is a challenge, where care has to be taken for both mother and fetus. There are specific physiologic changes that occur with pregnancy that have an impact on the anesthetic management of the mother. When providing maternal anesthesia, there is also an impact on the fetus, with concerns for potential negative side effects of the anesthetic regimen used. The question whether the fetus is capable of feeling pain is difficult to answer, but there are indications that nociceptive stimuli have a physiologic reaction. This nociceptive stimulation of the fetus also has the potential for longer-term effects, so there is a need for fetal analgesic treatment. The extent to which a fetus is influenced by the maternal anesthesia depends on the type of anesthesia, with different needs for extra fetal anesthesia or analgesia. When providing fetal anesthesia, the potential negative consequences have to be balanced against the intended benefits of blocking the physiologic fetal responses to nociceptive stimulation.
TL;DR: In about 40% of pregnancies, polyhydramnios remains unexplained during the course of pregnancy and in 10% of these cases, an anomaly will only be found after birth, antenatal characteristics do not help to detect these anomalies before birth.
Abstract: Objective: To investigate the proportion and type of fetal anomalies that are associated with polyhydramnios and to examine whether in cases with idiopathic polyh
TL;DR: Fetal complications are common after fetoscopic laser surgery in twin-to-twin transfusion syndrome and in this experience, an increasing number of procedures improved the performance of a new fetoscope laser center.
Abstract: Objective: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS). Methods: A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004–2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed. Results: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00–1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit. Conclusions: Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.
TL;DR: Myocardial strain reflects the changing physiology of fetal CHD, and speckle tracking might be a useful tool to study the progress of myocardial function in affected fetuses.
Abstract: Objectives: To compare myocardial deformation patterns in fetuses with congenital heart disease (CHD) with our reference range using speckle tracking echocardiogr
TL;DR: In TTTS, both the donor and the recipient exhibit abnormalities of myocardial tissue deformation with ventricle-specific changes evident based on loading conditions, which are both globally depressed with systolic and diastolic dysfunction.
Abstract: Objectives: Twin-twin transfusion syndrome (TTTS) is a complex disorder with altered cardiovascular loading conditions that affects both donors and recipients. My
TL;DR: In a provincial referral center with antenatal expectant management of CCAM, the CVR was associated with hydrops and postnatal outcome, with a CVR <0.56 predictive of good prognosis after birth.
Abstract: Objective: To determine whether the congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) is associated with fetal and postnatal outcome after prenatal diagnosis and
TL;DR: NIPD of fetal trisomy 21, using fetal nucleic acids in maternal plasma, appears to have a high diagnostic accuracy and large-scale prospective studies are awaited before implementation in clinical practice.
Abstract: Background: Both pregnant women and providers of obstetric care are aware of the rapid advances in noninvasive prenatal diagnosis (NIPD) of fetal trisomies, and appear to look forward to its clinical introduction. Objectives: To review and critically assess the published literature on diagnostic accuracy of NIPD using cell-free fetal DNA or RNA in maternal blood to detect fetal trisomy 21. Method: An electronic search was performed in MEDLINE, EMBASE and the Cochrane library (1997 to April 2011). Of a total of 201 citations, 9 studies were eligible for full-text analysis by 2 independent reviewers, using the QUADAS tool. Results: Two of the 9 analyzed studies complied with the criteria of the QUADAS tool. Combining the selected 2 studies, with a total of 681 pregnancies included, overall sensitivity was 125/125 (100%, 95% CI 97.5–100%) and specificity 552/556 (99.3%, 95% CI 98.7–99.3%). Conclusions: NIPD of fetal trisomy 21, using fetal nucleic acids in maternal plasma, appears to have a high diagnostic accuracy. Large-scale prospective studies are awaited before implementation in clinical practice.
TL;DR: Detailed exploration of the morphology of mitral and aortic valve closure and opening clicks shows how selection of different phases of these clicks may significantly influence the Mod-MPI.
Abstract: Objectives: To construct gestational age-adjusted reference ranges of the left fetal modified myocardial performance index (Mod-MPI) in the Australian population and assess the influence of valve click caliper position on constituent time intervals and the Mod-MPI. Methods: This is a prospective longitudinal study of 117 normal singleton fetuses undergoing 318 ultrasound scans at 4–6 weekly intervals between 18 and 38 weeks of gestation. The isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET) were measured at 3 different caliper positions in each fetus: beginning of the original valve clicks (‘original’), beginning of the reflected valve clicks (‘reflected’), and peak of valve clicks (‘peak’). The Mod-MPI was calculated as (ICT + IRT)/ET. Results: The Mod-MPI increased throughout gestation with means ± SD of 0.42 ± 0.05 ‘reflected’ and ‘peak’ versus 0.49 ± 0.03 ‘original’ at 19 weeks, and means of 0.46 ± 0.05 ‘reflected and peak’ versus 0.51 ± 0.08 ‘original’ at 36 weeks. Throughout gestation, ICT remained fairly constant and IRT increased, while ET decreased with ‘original’ click and remained constant for ‘reflected’ and ‘peak’ clicks. A modest increase in Mod-MPI was seen with increasing fetal heart rate. Analysis of repeatability for the 3 methods showed the following ICCs: ‘original’, 0.797 (95% CI 0.762–0.829); ‘reflected’, 0.809 (95% CI 0.775–0.839), and ‘peak’, 0.799 (95% CI 0.764–0.831). Conclusions: Detailed exploration of the morphology of mitral and aortic valve closure and opening clicks shows how selection of different phases of these clicks may significantly influence the Mod-MPI. We recommend that the peak of the valve clicks be standardized between research groups.
TL;DR: Digital PCR is potentially a cheaper methodology for trisomy 21, but it is too early to determine the optimal method.
Abstract: Objective: To determine the feasibility of digital PCR analysis for noninvasive prenatal diagnosis of trisomy 21. Methods: Through power equations, we modeled the number of wells necessary to determine the feasibility of digital PCR as a practical method for trisomy 21 risk assessment. Results: The number of wells needed is a direct correlate of the ability to isolate free fetal DNA. If a 20% fetal DNA enhancement can be achieved, then 2,609 counts would be sufficient to achieve a 99% detection rate for a 1% false-positive rate and potentially feasible with readily available plates. However, if only a 2% increase is seen, then 220,816 counts will be necessary, and over 110,000 would be needed just to achieve 95% for a 5% false-positive rate – both far beyond current commercially available technology. Conclusion: There are several noninvasive prenatal diagnostic methods which may reach commercialization; all have differing potential advantages and disadvantages. Digital PCR is potentially a cheaper methodology for trisomy 21, but it is too early to determine the optimal method.
TL;DR: 14 potential new biomarker candidates for preeclampsia were identified and validated 4 of them by quantitative RT-PCR and 2 of them with subsequent serum protein analyses, and the maternal plasma protein levels of 2 of these genes were confirmed to be significantly different between preeClampsia cases and controls.
Abstract: Introduction: Our aim was to identify novel biomarker candidates for the near-term prediction of preeclampsia in a homogenous collective. In this study, we screened at the genome-wide level for gene expression in placental villous tissue from patients with severe preeclampsia in comparison to normal healthy pregnancies. Material and Methods: Total RNA was extracted from placental villous tissue from 9 preeclamptic patients and 7 normotensive controls after scheduled cesarean sections. After sample pooling, gene expression analysis was performed using six Affymetrix Human Gene 1.0 ST arrays, followed by quantitative RT-PCR and validation of selected markers in the serum of patients at the protein level. Results: In total, 896 significantly differentially expressed genes were identified (p ≤ 0.05). After restricting these to molecules present in the circulation, 9 upregulated and 5 downregulated genes were selected. Four of them (β-hCG, HTRA4, LHB1, all upregulated; and NOX4, downregulated) were validated by quantitative real-time RT-PCR. Finally, the maternal plasma protein levels of 2 of these genes (LHB and β-hCG) were confirmed to be significantly different between preeclampsia cases and controls. Discussion: We identified 14 potential new biomarker candidates for preeclampsia and validated 4 of them by quantitative RT-PCR and 2 of them with subsequent serum protein analyses. Further studies will assess the optimal marker combination for the imminent prediction of impending preeclampsia.
TL;DR: Measurement of DV PIV improves the performance of first-trimester combined test for aneuploidies and in combination with fetal nuchal translucency thickness and serum free β-hCG and PAPP-A was estimated.
Abstract: Objective: To assess the value of ductus venosus pulsatility index for veins (DV PIV) in screening for aneuploidies at 11–13 weeks’ gestation. M