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Objective: α-klotho, a protein with anti-aging properties, has been involved in important biological processes, such as calcium/phosphate metabolism, resistance to oxidative stress, and nitric oxide production in the endothelium. Recent studies have suggested a role of α-klotho in endocrine regulation of mineral metabolism and postnatal growth in infants. Yet, the role of α-klotho during pregnancy remains largely unknown. The aim of this study was to determine whether maternal plasma concentration of α-klotho changes during pregnancy and evaluate its expression in pregnancies complicated by small for gestational age (SGA) and/or preeclampsia (PE)., Study Design: This cross-sectional study included patients in the following groups: (1) non pregnant women (n = 37); (2) uncomplicated pregnancy (n = 130); (3) PE without an SGA neonate (PE; n = 58); (4) PE with an SGA neonate (PE and SGA; n = 52); and (5) SGA neonate without PE (SGA; n = 52). Plasma concentrations of α-klotho were determined by ELISA., Results: The median plasma α-klotho concentration was higher in pregnant than in non-pregnant women. Among women with an uncomplicated pregnancy, the median plasma concentration of α-klotho increased as a function of gestational age (Spearman Rho = 0.2; p = 0.006). The median (interquartile range) plasma concentration of α-klotho in women with PE and SGA [947.6 (762-2013) pg/mL] and SGA without PE [1000 (585-1567) pg/mL] were 21% and 17% lower than that observed in women with an uncomplicated pregnancy [1206.6 (894-2012) pg/mL], (p = 0.005 and p = 0.02), respectively. Additionally, there were no significant differences in the median plasma concentration of α-klotho between uncomplicated pregnancies and women with PE without an SGA neonate (p = 0.5)., Conclusion: Maternal plasma concentration of α-klotho was higher during pregnancy than in a non-pregnant state. Moreover, the median maternal plasma concentration of α-klotho was lower in mothers who delivered an SGA neonate than in those with an uncomplicated pregnancy regardless of the presence or absence of PE.

Aim: To construct a normal value for inhibin-A concentrations at 14-20 weeks of gestation for a Thai population., Material and Methods: Inhibin-A concentrations from pregnant women without Down's syndrome at 14-20(+6) weeks of gestation were measured. Maternal serum inhibin-A levels were analyzed according to the gestational age., Results: Serum specimens from 727 Thai women were analyzed. Inhibin-A levels decreased from 14 to 17(+4) weeks and then gradually rose thereafter, giving a U-shape pattern., Conclusion: The data of inhibin-A concentration at 14-20 weeks of gestation for normal Thai pregnant women fitted well with quadratic regression., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

To compare the whole genomic microRNA (miRNA) between the selective fetal growth restriction (sFGR) twin and the normally growing (control) co-twin in monochorionic (MC) twin pregnancies. MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled by microarray. The ratio of the placental miRNA of the sFGR twin to that of the normally larger co-twin were calculated and compared to that of the control twin pairs. The miRNA microarray intensity amongst normal and sFGR large and small twins are shown. The expression data presented here will facilitate other researchers who are working on placental regulation and mechanism in pregnancy complicated by fetal growth restriction.The dataset supports the research article entitle “Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies” [1].

This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1– placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, β, θ i , and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1–placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1–placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1–placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62–106.16 vs soluble fms-like tyrosine kinase-1–placental growth factor ratio, 6.96; 95% confidence interval, 1.76–27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04–10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52–59.85 vs 7.09; 95% confidence interval, 3.74–13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1–placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67–33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41–14.35 vs soluble fms-like tyrosine kinase-1–placental growth factor ratio, 14.94; 95% confidence interval, 9.42–23.70). Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1–placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery. [ABSTRACT FROM AUTHOR]

The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks' gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different (p>0.05). There was no significant association between gestational age at delivery and log10 sFlt-1 and log10 sFlt-1 MoM (p>0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks' gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether gestational age at intervention (< or ≥ 16 weeks) and other factors affect the risk of loss of the cotwin after selective fetal reduction using radiofrequency ablation (RFA) in monochorionic (MC) pregnancy.Methods: This was a single-center retrospective analysis of 63 consecutive RFA procedures performed at our institution from January 2011 to October 2019 for selective fetal reduction in complicated MC pregnancies. Indications for RFA were twin reversed arterial perfusion sequence (13 cases), twin-to-twin transfusion syndrome (12 cases), twin anemia-polycythemia sequence (two cases), selective fetal growth restriction (10 cases), discordant anomalies (17 cases) and multifetal pregnancy reduction in triplets or quadruplets with a MC pair (nine cases). Twenty-six (41.3%) of these procedures were performed before and 37 (58.7%) after 16 weeks. Potential factors that could affect the risk of loss of the cotwin, including gestational age at RFA, order of multiple pregnancy, amnionicity, indication for RFA and number of ablation cycles, were assessed first by univariate analysis and then by multivariate analysis.Results: There were 17 (27.0%) cotwin losses. Ablation cycles numbering four or more was the only factor among those investigated to be associated with loss of the cotwin after RFA (P = 0.035; odds ratio, 5.21), while the indication for RFA, order of multiple pregnancy, amnionicity and gestational age at RFA had no effect. Comparing RFA performed at < 16 vs ≥ 16 weeks, there was no difference in the rate of cotwin loss (23.1% vs 29.7%; P = 0.558) or preterm prelabor rupture of the membranes before 34 weeks (7.7% vs 5.4%; P = 0.853), or in the median gestational age at delivery (36.2 vs 37.3 weeks; P = 0.706).Conclusions: RFA is a promising tool for early selective fetal reduction in MC pregnancy before 16 weeks. Four or more ablation cycles is a major risk factor for cotwin loss. Careful assessment pre- and post-RFA, together with proficient operative skills to minimize the number of ablation cycles, are the mainstay to ensure that this procedure is effective and safe. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective Data: Preconception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization, and organogenesis. Most studies have evaluated the potential benefit of preconception or early administration of low-dose aspirin in women with a history of recurrent pregnancy loss, women who have undergone in vitro fertilization, or women with thrombophilia or antiphospholipid syndrome. These women are at an increased risk of placenta-associated complications of pregnancy, including preeclampsia, preterm delivery, and fetal growth restriction.Study Outcomes: We performed a systematic review and meta-analysis to evaluate the effect of low-dose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction.Study Appraisal and Synthesis Methods: We searched in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from 1985 to November 2018. Entry criteria were randomized controlled trials evaluating the effect of aspirin administered at <11 weeks' gestation in preventing preeclampsia and/or hypertensive disorders in pregnancy or improving pregnancy outcomes in women with recurrent miscarriage as compared with placebo or no treatment and outcome data available or provided by authors for >85% of the study population. Relative risks with 95% confidence intervals were calculated for each study and pooled for global analysis as the effect measure. We assessed statistical heterogeneity in each meta-analysis using the χ2 statistics, I2, and Tau2. Heterogeneity was considered substantial if an I2 was greater than 50% and either the Tau2 was greater than zero or there was a low P value (<0.10) in the χ2 test for heterogeneity. Random-effects meta-analysis, weighted by the size of the studies, was performed to produce an overall summary on aspirin effect for each outcome. Sensitivity analysis by sequential omission of each individual study and by fixed-effects model was performed. Publication bias was not assessed because of the small number of included studies. Statistical analysis was performed using Stata release 14.0 (StataCorp).Results: The entry criteria were fulfilled by 8 randomized controlled trials on a combined total of 1426 participants. Low-dose aspirin initiated at <11 weeks' gestation was associated with a nonsignificant reduction in the risk of preeclampsia (relative risk, 0.52; 95% confidence interval, 0.23-1.17, P = .115), gestational hypertension (relative risk, 0.49; 95% confidence interval, 0.20-1.21; P = .121), and any hypertensive disorder of pregnancy (relative risk, 0.59; 95% confidence interval, 0.33-1.04, P = .067). Early administration of low-dose aspirin reduced the risk of preterm delivery (relative risk, 0.52; 95% confidence interval, 0.27-0.97, P = .040) but had no impact on the risk of fetal growth restriction (relative risk, 1.10; 95% confidence interval, 0.58-2.07, P = .775). Except for preterm delivery and any hypertensive disorder of pregnancy, sensitivity analysis demonstrated similar observations, therefore confirming the robustness of the analysis.Conclusion: The administration of low-dose aspirin at <11 weeks' gestation in women at high risk does not decrease the risk of preeclampsia, gestational hypertension, any hypertensive disorder of pregnancy, and fetal growth restriction. However, it might reduce the risk of preterm delivery. Larger randomized controlled trials will be required to substantiate the findings. [ABSTRACT FROM AUTHOR]

The study aimed to identify the simplest protocol for the measurement of mean arterial pressure (MAP) across 10-40weeks' gestation. 2726 women with uncomplicated singleton pregnancy attending for their routine hospital visit between 10 and 40weeks' gestation were recruited prospectively. The blood pressure (BP) was measured according to the National Heart Foundation of Australia (NHFA) protocol using automated devices. Linearizing regression models were determined for MAP derived from single, repeat and average measurements taken in the left and right arms using the same polynomial power of the best fit model determined using the NHFA protocol. Z-scores were used to compare the differences between the smoothed 50th percentiles. The first measurements taken in the left and right arms were on average 0.15SD and 0.12SD, respectively, higher than those obtained from the NHFA protocol. The second measurements taken in the left and right arms were both 0.26SD lower than the first measurement taken in the same arm and these values were lower than those from the NHFA protocol. The median MAP determined by the protocol of the average of two measurements taken in both arms was similar to the median MAP determined using the NHFA protocol (Z-score 0.0194SD). MAP derived by the average of two measurements in both arms had a quadratic relationship with gestation, with the measurement being the lowest in the mid-trimester. In conclusion, our study has demonstrated that at 10-40weeks' gestation, BP recordings can be obtained by a simpler protocol using the average of two measurements in both arms. [ABSTRACT FROM AUTHOR]

Background: Activation of the coagulation system and increased thrombin generation have been implicated in the pathophysiology of preeclampsia, and this rationale supports the administration of low-molecular-weight heparin to prevent this syndrome in patients at risk. Yet randomized trials of this prophylactic measure have yielded contradictory results. One possible explanation is that only a subset of patients with preeclampsia have excessive thrombin generation and would benefit from the administration of low-molecular-weight heparin. Therefore, the key questions are whether and when patients who subsequently develop preeclampsia present evidence of abnormal thrombin generation.Objectives: The objectives of the study were to determine 1) the kinetics of thrombin generation throughout gestation in women with a normal pregnancy and in those with early and late preeclampsia, and 2) the diagnostic performance of in vivo thrombin generation parameters to predict the development of preeclampsia.Study Design: This retrospective nested case-control study was based on a prospective longitudinal cohort of singleton gestations. Cases comprised women who developed preeclampsia (n=49) and controls consisted of patients with a normal pregnancy (n=45). Preeclampsia was classified into early onset (n=24) and late onset (n=25). The longitudinal changes in the parameters of the thrombin generation assay (lag time, time to peak thrombin concentration, peak thrombin concentration, endogenous thrombin generation, and velocity index) throughout gestation were compared between the study groups, and the normal pregnancy percentiles were derived from the control group. We tested whether a single parameter or a combination of parameters derived from the kinetics of thrombin generation could identify patients who subsequently developed preeclampsia. Time-related parameters <10th percentile were considered short, and concentration-related parameters >90th percentile were considered high.Results: 1) Patients who developed preeclampsia (early- and late-onset) had abnormal thrombin generation kinetics as early as 8-16 weeks of gestation; 2) patients with a combination of a short lag time and a high peak thrombin concentration at 8-16 weeks gestation had an odds ratio (OR) of 43.87 for the subsequent development of preeclampsia [area under the curve (AUC) 0.79; sensitivity 56.8%; specificity 92.7%; positive likelihood ratio 7.76]; 3) at 16-22 weeks of gestation, patients with a combination of a short lag time with a high velocity index had an OR of 16 for the subsequent development of preeclampsia (AUC 0.78; sensitivity 62.2%; specificity 92.5%; positive likelihood ratio 8.29).Conclusion: During early pregnancy, the thrombin generation assay can identify the subset of patients at greater risk for the development of preeclampsia due to accelerated and enhanced production of thrombin. This observation provides a rationale for testing the efficacy of low-molecular-weight heparin in this subset of patients. We propose that future research on the efficacy of low-molecular-weight heparin and other interventions targeting the coagulation system to prevent preeclampsia should be focused on patients with abnormal kinetics of thrombin generation. [ABSTRACT FROM AUTHOR]

Background: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known.Objective: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion.Study Design: This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion.Results: 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions.Conclusion: Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders. [ABSTRACT FROM AUTHOR]

To 1. investigate whether the serum soluble fms-like tyrosine kinase-1 (sFlt-1) at 11-14 weeks of gestation in pregnancies that subsequently develop pre-eclampsia (PE) is different from those without PE and 2. compare performance of the international prediction of pregnancy complications (IPPIC) reported models (maternal factors, systolic blood pressure (SBP), placental growth factor (PlGF) and sFlt-1) and the competing risk model (maternal factors, mean arterial pressure (MAP), PlGF) for predicting any-onset and late-onset PE (>=34 weeks). Median serum sFlt-1 level and its MoM were not significantly different between PE and no PE groups (p > 0.05). Conclusions No significant difference in the sFlt-1 levels between PE and no PE was observed. [Extracted from the article]

Results Among 171 included pregnancies, 147 (86%) pregnancies progressed to beyond 13 weeks of gestation whereas 24 (14%) pregnancies resulted in a miscarriage during the first trimester. To evaluate the performance of a combination of maternal factors, ultrasound and biochemical markers at 6 weeks of gestation in the prediction of subsequent miscarriage prior to 13 weeks of gestation among singleton pregnancies resulting from I in-vitro i fertilisation/embryo transfer (IVF/ET). VP01.09: Biomarkers at six-week gestation in the prediction of early miscarriage in pregnancy resulting from assisted reproductive technology. [Extracted from the article]

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. Early-onset disease requiring preterm delivery is associated with a higher risk of complications in both mothers and babies. Evidence suggests that the administration of low-dose aspirin initiated before 16 weeks' gestation significantly reduces the rate of preterm preeclampsia. Therefore, it is important to identify pregnant women at risk of developing preeclampsia during the first trimester of pregnancy, thus allowing timely therapeutic intervention. Several professional organizations such as the American College of Obstetricians and Gynecologists (ACOG) and National Institute for Health and Care Excellence (NICE) have proposed screening for preeclampsia based on maternal risk factors. The approach recommended by ACOG and NICE essentially treats each risk factor as a separate screening test with additive detection rate and screen-positive rate. Evidence has shown that preeclampsia screening based on the NICE and ACOG approach has suboptimal performance, as the NICE recommendation only achieves detection rates of 41% and 34%, with a 10% false-positive rate, for preterm and term preeclampsia, respectively. Screening based on the 2013 ACOG recommendation can only achieve detection rates of 5% and 2% for preterm and term preeclampsia, respectively, with a 0.2% false-positive rate. Various first trimester prediction models have been developed. Most of them have not undergone or failed external validation. However, it is worthy of note that the Fetal Medicine Foundation (FMF) first trimester prediction model (namely the triple test), which consists of a combination of maternal factors and measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has undergone successful internal and external validation. The FMF triple test has detection rates of 90% and 75% for the prediction of early and preterm preeclampsia, respectively, with a 10% false-positive rate. Such performance of screening is superior to that of the traditional method by maternal risk factors alone. The use of the FMF prediction model, followed by the administration of low-dose aspirin, has been shown to reduce the rate of preterm preeclampsia by 62%. The number needed to screen to prevent 1 case of preterm preeclampsia by the FMF triple test is 250. The key to maintaining optimal screening performance is to establish standardized protocols for biomarker measurements and regular biomarker quality assessment, as inaccurate measurement can affect screening performance. Tools frequently used to assess quality control include the cumulative sum and target plot. Cumulative sum is a sensitive method to detect small shifts over time, and point of shift can be easily identified. Target plot is a tool to evaluate deviation from the expected multiple of median and the expected median of standard deviation. Target plot is easy to interpret and visualize. However, it is insensitive to detecting small deviations. Adherence to well-defined protocols for the measurements of mean arterial pressure, uterine artery pulsatility index, and placental growth factor is required. This article summarizes the existing literature on the different methods, recommendations by professional organizations, quality assessment of different components of risk assessment, and clinical implementation of the first trimester screening for preeclampsia. [ABSTRACT FROM AUTHOR]

Pregnancies conceived by I in vitro i fertilisation (IVF) have increased risk of placental associated complications (PACs). The objective of this study is to evaluate maternal BP and UtA-PI profiles in IVF pregnancies with and without PACs. Conclusions Women with IVF pregnancies who subsequently develop PACs have higher maternal BP, but not UtA-PI, than those without complications. [Extracted from the article]

EP08.07: Measurement of Sylvian fissure angles at 18-30 weeks' gestation in cases with neuronal migration disorder To investigate Sylvian fissure angle in cases with neuronal migration disorder comparing to normal reference range. Sylvian fissure angle may be one of convincing evidences which indicate neuronal migration disorder between 18 and 25 weeks when gyri and sulci are not conspicuous on the brain surface. [Extracted from the article]

Objective: Pregnancy is accompanied by dramatic physiological changes in maternal plasma proteins. Characterization of the maternal plasma proteome in normal pregnancy is an essential step for understanding changes to predict pregnancy outcome. The objective of this study was to describe maternal plasma proteins that change in abundance with advancing gestational age and determine biological processes that are perturbed in normal pregnancy.Study Design: A longitudinal study included 43 normal pregnancies that had a term delivery of an infant who was appropriate for gestational age without maternal or neonatal complications. For each pregnancy, 3 to 6 maternal plasma samples (median, 5) were profiled to measure the abundance of 1125 proteins using multiplex assays. Linear mixed-effects models with polynomial splines were used to model protein abundance as a function of gestational age, and the significance of the association was inferred via likelihood ratio tests. Proteins considered to be significantly changed were defined as having the following: (1) >1.5-fold change between 8 and 40 weeks of gestation; and (2) a false discovery rate-adjusted value of P < .1. Gene ontology enrichment analysis was used to identify biological processes overrepresented among the proteins that changed with advancing gestation.Results: The following results were found: (1) Ten percent (112 of 1125) of the profiled proteins changed in abundance as a function of gestational age; (2) of the 1125 proteins analyzed, glypican-3, sialic acid-binding immunoglobulin-type lectin-6, placental growth factor, C-C motif-28, carbonic anhydrase 6, prolactin, interleukin-1 receptor 4, dual-specificity mitogen-activated protein kinase 4, and pregnancy-associated plasma protein-A had more than a 5-fold change in abundance across gestation (these 9 proteins are known to be involved in a wide range of both physiological and pathological processes, such as growth regulation, embryogenesis, angiogenesis immunoregulation, inflammation etc); and (3) biological processes associated with protein changes in normal pregnancy included defense response, defense response to bacteria, proteolysis, and leukocyte migration (false discovery rate, 10%).Conclusion: The plasma proteome of normal pregnancy demonstrates dramatic changes in both the magnitude of changes and the fraction of the proteins involved. Such information is important to understand the physiology of pregnancy and the development of biomarkers to differentiate normal vs abnormal pregnancy and determine the response to interventions. [ABSTRACT FROM AUTHOR]

Background: Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately 1 of every 7 pregnancies, but only 5% of neonates exposed to MSAF develop MAS. Why some infants exposed to meconium develop MAS while others do not is a fundamental question. Patients with MSAF have a higher frequency of intraamniotic inflammation/infection than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF.Objective: We sought to investigate whether intraamniotic inflammation and funisitis, the histopathologic landmark of a fetal inflammatory response, predispose to MAS.Study Design: A prospective cohort study was conducted from 1995 through 2009. Amniotic fluid (AF) samples (n = 1281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intraamniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 was >23 ng/mL. Funisitis was diagnosed by histologic examination if inflammation was present in the umbilical cord.Results: The prevalence of MSAF was 9.2% (118/1281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each P > .1). Mothers whose newborns developed MAS had a higher median of AF matrix metalloproteinase-8 (456.8 vs 157.2 ng/mL, P < .05). Newborns exposed to intraamniotic inflammation had a higher rate of MAS than those who were not exposed to intraamniotic inflammation [13.0% (10/77) vs 0% (0/32), P = .03], as did those exposed to funisitis [31.3% (5/16) vs 7.3% (6/82); relative risk, 4.3; 95% confidence interval, 1.5-12.3]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intraamniotic inflammation and funisitis than in those without intraamniotic inflammation and funisitis [28.6% (4/14) vs 0% (0/28), P = .009], while the rate of MAS did not show a significant difference between patients with intraamniotic inflammation alone (without funisitis) and those without intraamniotic inflammation and funisitis [10.9% (5/46) vs 0% (0/28)].Conclusion: The combination of intraamniotic inflammation with fetal systemic inflammation is an important antecedent of MAS. This concept has implications for the understanding of the mechanisms of disease responsible for MAS and for the development of prognostic models and therapeutic interventions for this disorder. [ABSTRACT FROM AUTHOR]