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Objectives: Early identification of preeclampia in the first trimester of pregnancy represents one of the major challenges of modern fetal medicine. The primary aim of our study was to evaluate the effectiveness of implementation of preeclampsia screening in Tuscany, Italy. The secondary aim was to evaluate pregnancy/neonatal outcome in the positive screening group compared with the negative screening group.Study Design: Retrospective study including singleton pregnancies undergoing screening for preeclampsia. The screening test was a multiparametric algorithm based on maternal history, biochemical and biophysical parameters (Fetal Medicine Foundation algorithm).Main Outcome Measures: The overall performance of the test was calculated, in terms of sensitivity, specificity, positive and negative predictive value and in relation to gestational age at onset (primary aim). Pregnancy and neonatal outcomes were then compared between the positive and negative population at preeclampsia screening test (secondary aim).Results: Of the 5719 patients enrolled, 4797 were included in the analysis. The sensitivity for early onset of preeclampsia (≤34 weeks) was 0.75 (CI:0.41-0.93) and specificity 0.93 (CI:0.92-0.94) for a false positive rate of 7%. The population that tested positive for preeclampsia screening showed a higher incidence of deliveries at lower gestational ages (p < 0.001), preeclampsia onset despite prophylaxis with aspirin (p < 0.001), emergency caesarean section (p < 0.001), low fetal birth weight (p < 0.001) and neonatal admission in intensive care unit (p < 0.001).Conclusions: Our data confirm the validity of first trimester screening test in identifying a category of patients at greatest risk for preeclampsia even in the presence of a post-test pharmacological prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).Methods: A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).Results: In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.Discussion: In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.Conclusion: In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion. [ABSTRACT FROM AUTHOR]

Objective To examine the potential role of maternal serum levels of tumor necrosis factor-α (TNF-α) and high sensitivity C-reactive protein (Hs-CRP) in the first trimester of pregnancy in the prediction of gestational diabetes mellitus (GDM). Methods Maternal serum TNF-α and Hs-CRP concentrations were measured in a case–control study of singleton pregnancies at 11–13 weeks' gestation, which included 200 cases that subsequently developed GDM and 800 unaffected controls. Measured levels of TNF-α and Hs-CRP were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and history. The performance of screening for GDM by maternal factors and MoM values of TNF-α and Hs-CRP was evaluated by the area under the receiver operating characteristic curves (AUROC). Results In the GDM group, compared to the normal group, the median TNF-α was significantly increased (1.303 MoM, interquartile range [IQR] 1.151–1.475 vs. 1.0 MoM, IQR 0.940–1.064; p = 0.031) and the median Hs-CRP was not significantly different (1.113 MoM, IQR 0.990–1.250 vs. 1.0 MoM, IQR 0.943–1.060; p = 0.084). In the prediction of GDM, the AUROC for maternal characteristics with TNF-α or Hs-CRP was not significantly different than the AUROC for maternal characteristics alone (p = 0.5055 and p = 0.2197, respectively). Conclusions In pregnancies that develop GDM there is no evidence of an inflammatory response at 11–13 weeks’ gestation and the levels of serum TNF-α and Hs-CRP are not useful in first-trimester screening for GDM. [ABSTRACT FROM AUTHOR]

Objective To investigate whether first-trimester biochemical markers of placentation, including pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF), are altered in women that subsequently develop gestational diabetes mellitus (GDM) and to examine their potential value in improving the performance of screening for GDM by maternal characteristics and medical history. Methods The study population of 31,225 singleton pregnancies, including 787 cases that developed GDM, was drawn from women undergoing routine prospective screening for pregnancy complications at 11–13 weeks’ gestation. Maternal serum PAPP-A and PLGF were measured and the levels were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and medical history. The performance of screening for GDM by maternal factors and MoM values of PAPP-A and PLGF was evaluated by receiver operating characteristic (ROC) curves. Results In the GDM group, compared to the unaffected group, the median PAPP-A was reduced (0.949, 95% CI 0.913–0.987 MoM) (p = 0.0009) and median PLGF was increased (1.053, 95% CI 1.023–1.083 MoM) (p = 0.004). The performance of screening for GDM by maternal factors was not improved by the addition of PAPP-A and/or PLGF. Conclusions First trimester maternal serum PAPP-A and PLGF are not useful in screening for GDM. [ABSTRACT FROM AUTHOR]

Objective To examine maternal serum concentrations of placental growth factor (PlGF) at 11–14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Methods Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal–pregnancy characteristics were analyzed. Results Log 10 transformed PlGF (log 10 PlGF) was not related to maternal factors. Log 10 PlGF was increased (p = 0.008) in the GDM group compared to the control group. Log 10 PlGF was associated with fasting glucose levels (p = 0.04) in the oral glucose tolerance test. Log 10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC) = 0.73, p < 0.001]. Log 10 PlGF alone was a significant predictor of GDM (AUC = 0.63, p < 0.001). Combination of maternal weight, maternal age and log 10 PlGF resulted in an improved prediction (DR = 71.4%, for 25% FPR, AUC = 0.78, Model R 2 = 0.17, p < 0.001). Conclusion At 11–14 weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11–14 weeks improves the performance of early screening for GDM provided by maternal factors alone. [ABSTRACT FROM AUTHOR]

Objectives: to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. Methods: a retrospective validation of firsttrimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11+0 and 13+6 weeks of gestation, between April 2007 and December 2008. Results: of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. Conclusion: in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. [ABSTRACT FROM AUTHOR]

Summary: There have been tremendous advancements over the past three decades in prenatal screening for aneuploidy and we have changed our practice from screening by maternal age alone to ‘combined’ first trimester screening and circulating cell-free fetal DNA. We currently use the nuchal translucency and biochemical markers of free β-hCG and PAPP-A to determine the risk of fetal aneuploidy. The primary goal is to identify higher risk women for fetal aneuploidy early in pregnancy and give them the option to pursue invasive testing in a timely manner if desired. [Copyright &y& Elsevier]

Abstract: Preconceptual and prenatal counseling recommendations have changed significantly over the past 12 months. Since January 2007, two new prenatal screening and testing practice bulletins have been published by the American College of Obstetrics and Gynecologists (ACOG).1,2 These changes are substantive and impact every clinician providing counseling to women who are pregnant or are considering pregnancy. These recommendations are also changing the prenatal experience for women; they will certainly notice the difference if this is not their first pregnancy. Clinicians must be prepared to answer patient questions, provide accurate information, and order the correct tests at the appropriate times. This article reviews the recent screening recommendations and describes the advantages and limitations of the screening tests. [Copyright &y& Elsevier]

Objective: The purpose of this study was to evaluate whether there is a nuchal translucency (NT) measurement, independent of gestational age, above which immediate diagnostic testing should be offered without waiting for first trimester serum markers. Studs, design: Thirty-six thousand one hundred twenty patients had successful measurement of simple NT at 10 3/7 to 13 6/7 weeks and had first trimester serum screening. No risks were reported until second trimester serum screening was completed. Results: Thirty-two patients (0.09%) had NT ≥4.0 ram; the lowest combined first trimester trisomy 21 risk assessment in euploid cases was 1 in 8 and among aneuploidy cases was 7 in 8. One hundred twenty-eight patients (0.3%) had simple NT ≥ 3.0 mm: the lowest combined first trimester trisomy 21 risk assessment of any patient in this group was 1 in 1479 and the lowest risk assessment among aneuploid cases was 1 in 2. Ten patients (8%) had first trimester trisomy 21 risk assessments lowered to less that 1:200 and none of these 10 cases had an abnormal outcome. Conclusion: During first trimester Down syndrome screening, whenever an NT measurement of 3.0 mm or greater is obtained there is minimal benefit in waiting for serum screening results, and no benefit for NT of 4.0 mm or greater. Differentiation between cystic hygroma and enlarged simple NT (≥3.0 mm) is now a moot point as both are sufficiently high risk situations to warrant immediate CVS. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the value of performing a detailed examination of the fetus as part of the routine 11 to 14 weeks' ultrasound scan in a 2-stage screening process for major structural defects in low-risk pregnancies. Study design: This was a prospective study in 1148 singleton pregnancies at 11 to 14 weeks of gestation using a combination of transabdominal and transvaginal sonography to estimate the sensitivity of the first and second trimester ultrasound scan in the detection of major anomalies. Results: Seven of the 14 major anomalies were detected at the 11 to 14 weeks scan, and an additional 6 at the second trimester scan. The sensitivity of the early anatomic examination and the overall sensitivity of the 2-stage screening were 50% and 92.8%, respectively. Nuchal translucency was increased in 5 of the 14 (35.7%) abnormal fetuses and in 1 of the 4 cases (25%) with major heart defects. Conclusion: Detailed, structured examination of fetal anatomy during the routine 11 to 14 weeks' scan can detect half of major structural defects in low-risk pregnancies. [ABSTRACT FROM AUTHOR]

The goal of first trimester screening for aneuploidy is to provide patients their risk assessment for fetal Down syndrome. Nonetheless, it has been noted that combined screening offers physicians and patients other important pregnancy information. For example, first trimester ultrasound results in accurate pregnancy dating and enables the early diagnosis of multiple gestations during the period when amnionicity and chorionicity is best discerned. It also detects a limited number of fetal anatomical abnormalities, affording patients time to make decisions regarding the management of their pregnancies. A cystic hygroma, one of the most powerful ultrasound markers for fetal aneuploidy, can be detected on first trimester ultrasound. An enlarged nuchal translucency may identify fetuses at risk for other adverse outcomes and for congenital heart defects. In addition, abnormal first trimester serum markers are associated with adverse pregnancy outcomes, and knowledge of these abnormalities may help with patient counseling and management. [Copyright &y& Elsevier]

The incidence of twins, triplets, and high-order multiples has increased substantially in the last two decades secondary to fertility treatments and to delayed childbearing. Prenatal diagnosis in these patients is challenging. Options for screening tests are limited. First trimester screening for Down syndrome in patients with multiples appears promising. This paper will review the advantages of first trimester screening in this high-risk patient population. [Copyright &y& Elsevier]

First trimester nuchal translucency ultrasound has evolved from an ultrasound measurement used only in a research setting to a screening tool which is being offered to the general obstetric population. Studies of nuchal translucency suggest great variation in Down syndrome detection rates which may be secondary to significant differences in sonographic training and nuchal translucency image quality. Inaccurate screening has the potential to adversely impact patients. This paper will explore: (1) why quality review in nuchal translucency ultrasound is important, (2) methods of nuchal translucency quality assessment, (3) experience with quality review in the research setting, and (4) current strategies for quality assessment in patient care. [Copyright &y& Elsevier]

There is extensive evidence that effective screening for major chromosomal abnormalities can be provided in the first trimester of pregnancy. Randomized studies have established that the risk of miscarriage from chorionic villus sampling in the first trimester is the same as for amniocentesis in the second trimester. Prospective studies have demonstrated that screening by a combination of fetal nuchal translucency (NT) and maternal serum free-β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) can identify 90% of fetuses with trisomy 21 and other major chromosomal abnormalities for a false-positive rate of 5%. This is superior to the 30% detection rate achieved by maternal age and 65% by second-trimester maternal serum biochemistry. A further improvement in the effectiveness of first-trimester screening is likely to be achieved by a risk-orientated two-stage approach. In this, the patients are subdivided into a high-risk group, requiring invasive testing, a low-risk group, which can be reassured that an abnormality is unlikely, and an intermediate-risk group (risk of 1 in 101 to 1 in 1000), in which further assessment is performed by first-trimester ultrasound examination (for presence/absence of the nasal bone or presence/absence of tricuspid regurgitation or normal/abnormal Doppler velocity waveform in the ductus venosus), and chorionic villus sampling is performed if their adjusted risk becomes 1 in 100 or more. As with all aspects of good clinical practice, those performing first-trimester scans should be appropriately trained and their results subjected to external quality assurance. This process was well established by the Fetal Medical Foundation several years ago and is widely accepted internationally. [Copyright &y& Elsevier]

Purpose: To develop a cost-effectiveness analysis model from the perspective of Medicare reimbursement to evaluate the costs and potential risks involved in performing second-trimester genetic sonography following the first-trimester sonographic measurement of nuchal translucency and serology for Down syndrome screening.Methods: Three clinical screening algorithms were constructed that detailed the diagnostic evaluation of the target population by using first-trimester or second-trimester ultrasound and appropriate serologies or first-trimester and second-trimester screening in combination. The cost analysis was then created by using a computer spreadsheet program by applying Medicare reimbursement, the prevalence of Down syndrome, and reported sensitivities of first-trimester and second-trimester ultrasound and analytes for Down syndrome for each clinical algorithm. Medicare Current Procedural Terminology codes, total relative value units, and payments for first-trimester and second-trimester ultrasound, chorionic villous sampling, amniocentesis, and serum analytes were obtained from the Medicare Part B Washington 2002 Provider Disclosure Report.Results: At any given prevalence of Down syndrome, first-trimester screening is always slightly less expensive to society than the other two models for both total cost and cost to diagnose each case of Down syndrome. Even if second-trimester screening were 100% sensitive, the sensitivity of first-trimester screening would have to fall below 55% for model 2 to be cheaper than model 1. Combining both first-trimester and second-trimester screening was substantially more expensive than models 1 or 2. More iatrogenic fetal deaths occur with combined screening than with either first or second trimester screening alone.Conclusions: Screening using first-trimester ultrasound and serologic markers to screen for Down syndrome is always slightly less expensive to society than second-trimester serologic and ultrasound screening. However, there is a significantly increased risk for iatrogenic fetal death if second-trimester genetic sonography is performed following normal first-trimester screening using currently accepted risk ratios. Patients should be counseled appropriately with this information, because an individual’s circumstances will affect that person’s perception of risk and subsequently affect his or her decision making. [Copyright &y& Elsevier]

Background: Preeclampsia affects approximately 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and death. In the last decade, extensive research has been devoted to early screening for preeclampsia with the aim of reducing the prevalence of the disease through pharmacologic intervention in the high-risk group starting from the first trimester of pregnancy.Objective: The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history (maternal factors) and biomarkers.Study Design: The data for this study were derived from prospective screening for adverse obstetric outcomes in women who attended for their routine first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in England. We screened 35,948 singleton pregnancies that included 1058 pregnancies (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A, and placental growth factor multiple of the median values. Five-fold cross validation was used to assess the performance of screening for preeclampsia that delivered at <37 weeks gestation (preterm-preeclampsia) and ≥37 weeks gestation (term-preeclampsia) by models that combined maternal factors with individual biomarkers and their combination with screening by maternal factors alone.Results: In pregnancies that experienced preeclampsia, the values of uterine artery pulsatility index and mean arterial pressure were increased, and the values of serum pregnancy-associated plasma protein-A and placental growth factor were decreased. For all biomarkers, the deviation from normal was greater for early than late preeclampsia; therefore, the performance of screening was related inversely to the gestational age at which delivery became necessary for maternal and/or fetal indications. Combined screening by maternal factors, uterine artery pulsatility index, mean arterial pressure, and placental growth factor predicted 75% (95% confidence interval, 70-80%) of preterm-preeclampsia and 47% (95% confidence interval, 44-51%) of term-preeclampsia, at a false-positive rate of 10%; inclusion of pregnancy-associated plasma protein-A did not improve the performance of screening. Such detection rates are superior to the respective values of 49% (95% confidence interval, 43-55%) and 38% (34-41%) that were achieved by screening with maternal factors alone.Conclusion: Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to describe the assessment of lower segment uterine scar (LSCS) by transvaginal ultrasound (TVUS) during a first-trimester scan. Study Design: Patients with a history of LSCS were prospectively enrolled over a 6 month period. Four groups were defined: type 1A, thin scar within cervicoisthmic canal (CIC); type 1B, thin above the internal os (IO); type 2A, dehiscent within the CIC; type 2B, dehiscent above the IO. Accuracy of first-trimester TVUS was investigated by blind testing a panel of 14 operators over a web-based dataset. Results: The scar was visualized in 122 of 123 patients enrolled. Types 1A, 1B, 2A, and 2B occurred in 49.2%, 3.3%, 38.3%, and 9.2%, respectively. When blind tested, fetal medicine specialists achieved a median sensitivity of 82% and specificity of 100% for the detection of a scar. These were 83% and 87% for nonspecialists. Conclusion: First-trimester uterine scar assessment may become a valuable tool in early recognition of patients at risk of subsequent perinatal complications. [ABSTRACT FROM AUTHOR]