Multiples Of Median Research Articles

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in small-for-gestational age fetuses at term.

To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in small-for-gestational-age (SGA) fetuses at term. In this retrospective single-center study 97 patients with singleton SGA fetuses at term (≥ 37 + 0weeks' gestation) were examined. Inclusion criteria were a birth weight < 10th centile, cephalic presentation and planned vaginal birth. Only cases with available Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) with calculated cerebroplacental ratio (CPR) in combination with a computerized CTG (cCTG) and STV 72h prior to delivery were eligible for analysis. Pulsatility indices (PI) were converted into multiples of median (MoM), adjusted for gestational age. The association between Doppler indices and STV values with mode of delivery [secondary cesarean delivery (CD), operative vaginal delivery (OVD), as well as secondary CD and OVD due to fetal distress] and neonatal outcome [UA blood pH ≤ 7.15 and the need of admission to the neonatal intensive care unit (NICU)] was analyzed using logistic regression analysis. There was a significant association between UA PI MoM and the rate of CD. CD due to fetal distress, OVD and OVD due to fetal distress did not show a correlation with the evaluated Doppler parameters. Furthermore, we did not find an association between low UA birth pH and Doppler parameters while neonates with the need of admission to NICU had significant higher UA PI MoM and significant lower MCA PI MoM and CPR MoM. Regarding STV, a significant effect of low STV on NICU admission was found while none of the other assessed outcome parameters were significantly associated with STV. STV and Doppler parameters in SGA fetuses at term are significantly associated to the rate of NICU admission.

Spontaneous and in vitro fertilization pregnancies have comparable first trimester screening profiles for Down syndrome

Objective:We aimed to compare the first trimester screening profiles of spontaneous (n=972) and in in vitro fertilization (IVF) pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, body mass index, and ethnicity.Material and Methods:A non-interventional analysis of retrospective cohort data and review of the literature.Results:All IVF pregnancies were achieved via intracytoplasmic sperm injection using the same ovarian stimulation protocol with recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of pregnancy-associated plasma protein-A (PAPP-A) were slightly lower in the fresh (1.19±0.6 vs 1.33±0.7, respectively; p=0.056) and frozen embryo transfer (1.03±0.5 vs 1.33±0.7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and beta-human chorionic gonadotrophin (β-hCG), and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of β-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies.Conclusion:These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous onceptions.

A risk prediction model for fetal hypospadias by testing maternal serum AFP and free beta-HCG

ObjectiveWe aimed to determine the correlation between serum alpha-fetoprotein (AFP), the free human chorionic gonadotropin beta subunit (free beta-HCG) in pregnant women during the mid-trimester, and fetal hypospadias, and tried to establish a risk prediction model. MethodsA multi-center case-control study was conducted. We divided the fetuses into two groups (69 with fetal hypospadias and 62 without fetal hypospadias). Time-resolved immunofluorescence was used to determine the serum levels of AFP and free beta-HCG. The best cut -value and area under curve (AUC) were determined based on the Receiver operating characteristics (ROC) curve, and the diagnostic value of AFP and free beta-HCG was evaluated. ResultsThe level of AFP in the study group was 1.14 multiple of Median(MOM), which was higher than in the control group (0.96 MOM); the difference was significant (Z = 2.831, P = .005). Similarly, the free beta-HCG level was 1.30 MOM in the study group, and was also significantly higher than in the control group (0.84 MOM; Z = 3.131, P = .004). We used the AFP and free beta-HCG levels separately to predict fetuses with hypospadias, and the AUCs were 0.644 (95% Confidence interval (CI): 0.5500.737, P = .005) and 0.659 (95% CI: 0.5650.752, P = .002), respectively. According to the ROC curve, the best cut-off values for AFP and free beta-HCG were 0.945 MOM and 1.275 MOM, respectively. When we combined the AFP level with the free beta-HCG level, the AUC was 0.700 (95% CI: 0.610–0.789, P < .001), with a sensitivity of 0.551 and a specificity of 0.855. ConclusionCombined screening for fetal hypospadias with maternal serum AFP and free beta-HCG levels during the early second trimester has high sensitivity and specificity, which can be used as a new marker.

Advances in perioperative management of intrauterine blood transfusion

With the fast development of fetal medicine in China, intrauterine transfusion, which is regarded as an effective treatment in certain conditions, has attracted more and more attention. In addition to the common seen red blood cell alloimmunization, the indications of intrauterine transfusion include parvovirus B19 infection, maternal-fetal blood transfusion syndrome, twin anemia-polycythemia sequence, placental chorionic hemangiomas and fetal sacrococcygeal teratomas. The recommended approach for intrauterine transfusion is umbilical vein or intraperitoneal transfusion depending on the gestational age, placental location, and presence of absence of fetal edema. However, umbilical artery and intracardiac transfusion are not recommended. In order to reduce the complications of intrauterine transfusion, routine fetal analgesia, avoidance of umbilical artery puncture and prior use of intrahepatic umbilical vein transfusion are recommended. Fetal middle cerebral artery-peak systolic velocity (MCA-PSV) >1.5 multiple of median (MOM) and 1.69 MOM can be a good indicators for the first and second intrauterine transfusions, respectively. For the third and subsequent transfusions, the rate of fetal hemoglobin decline is recommended to predict the timing of transfusion. Key words: Blood transfusion, intrauterine; Perioperative period; Fetal hemoglobin

Prediction of ischemic placental diseases during the first trimester combined test period: a retrospective cohort of low-risk pregnancies in search of the link between parity and disease

Objective: To assess the predictive power of a multifactorial model established on maternal characteristics, placenta-associated plasma protein A (PAPPA), and the mean uterine artery pulsatility index (Ut A PI) levels for the development of ischemic placental diseases (IPD) during the first-trimester combined test (FTCT) period and to evaluate the strength of some generally accepted clinical risk factors.Method: The studied data were obtained from a retrospective cohort of low-risk singleton pregnancies in the FTCT between 1 August 2016 and 1 December 2017. After routine 11–13-week examinations for FTCT, the Ut A PI was measured and stored electronically. The PAPPA multiple of median (MoM) was obtained as a routine component of aneuploidy screening.Results: A sample of 2493 pregnancies with clearly documented outcomes was studied. Early-onset preeclampsia, late-onset preeclampsia and fetal growth restriction (FGR) were observed in 9 (0.36%), 27 (1.08%), and 41 (1.64%) cases, respectively. With optimum cut-off levels of 0.69 for PAPPA MoM and 2.05 for mean Ut A PI and a false positive rate of 4.9%, IPD cases could be predicted with 83.3% sensitivity and 73.7% specificity. Nulliparity, previous abortion in nulliparous women and first pregnancy from second marriage were not independent risk factors. Maternal age, an interval from the last delivery longer than 6 years, and body mass index were found to be independent risk factors.Conclusion: The IPD showed some common and distinct clinical, laboratory and Doppler findings during the FTCT and were predictable with the help of multifactorial analysis. Some widely accepted risk factors could be affected by various confounders. Because of the increased IPD frequencies, parous women with a time interval from the last delivery of 6 years or longer should be screened as a high-risk group for placental dysfunction-related diseases.

Second Trimester Biochemical Markers as Possible Predictors of Pathological Placentation: A Retrospective Case-Control Study

Objective: We aimed to evaluate the association between second trimester biochemical markers and pathological placentation. Methods: This was a retrospective case-control study (2007–2014) of singleton gestations at a university-affiliated tertiary center. Women with pathologic placentation were subdivided into three groups: placenta accreta (group A), placenta previa (group B), or both (group C). We compared second trimester biochemical screening markers taken between 16 + 0 and 19 + 6 weeks of gestation between groups A, B, and C, and women with normal placentation (group D). Obstetrical and neonatal outcomes, risk factors for pathologic placentation, and second trimester biochemical marker values were compared between groups. Results: Overall, 301 deliveries were evaluated: 64 (21%) in group A, 66 (22%) in group B, 17 (6%) in group C, and 153 (51%) in group D. Each of the pathological placentation groups individually had a higher median alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) multiples of median (MoM) than the controls, with the highest values of AFP and hCG observed among women with placenta accreta and the lowest values among the controls. When a multivariant analysis was applied, the hCG levels remained significantly correlated with pathological placentation. Receiver operation characteristic curves for AFP, hCG, or both were computed. For AFP the area under the ROC curve (AUC) was 0.573 (95% CI 0.515–0.630, p < 0.0274) and a cut-off value above 0.99 MoM demonstrated a sensitivity and specificity of 71 and 46%, respectively, for the prediction of pathological placentation. For hCG, the AUC was 0.662 (95% CI 0.605–0.715, p < 0.0001) and a cut-off value of 1.25 MoM demonstrated a sensitivity and specificity of 53 and 68%. When both markers were plotted, the AUC was 0.668 (95% CI 0.611–0.721, p < 0.0001) and sensitivity and specificity were 63 and 64%, respectively. A percentile MoM cut-off approach distinguished between two groups: a high-risk group (patients with AFP or hCG or both above the 75th percentile, odds ratio (OR) for pathological placentation 2.27, 95% CI 1.42–3.63), and a low-risk group (patients with AFP or hCG or both below the 25th percentile, OR for pathological placentation 0.38, 95% CI 0.24–0.60). Conclusion: Second trimester biomarkers such as hCG and AFP can be used to raise a suspicion towards characterizing women into high-risk and low-risk groups for pathological placentation.

Factors associated with common and atypical chromosome abnormalities after positive combined first-trimester screening in Chinese women: a retrospective cohort study

BackgroundWhen cell-free DNA (cfDNA) testing is used as a secondary screening tool following combined first-trimester screening (cFTS), cFTS is used to estimate the prior risk for chromosome abnormalities. This study aimed to assess the factors that are associated with common and atypical abnormalities following cFTS, including cFTS risk, advanced maternal age, increased nuchal translucency (NT) ≥3.5 mm, and abnormal levels of serum markers.MethodsWe reviewed a historical cohort of 1855 Chinese women carrying singleton pregnancies with a positive cFTS [at a threshold of 1:250 for trisomy (T) 21 or 1:180 for T18] in one public hospital over a five-year period. All chromosome abnormalities were confirmed by invasive prenatal diagnosis (IPD) with karyotyping, with or without array comparative genomic hybridization. Using multivariable binary logistic regression analysis, we determined the parameters that were associated with common and atypical abnormalities.ResultsOverall, the prevalence of common and atypical abnormalities was 6.2 and 1.2%, respectively, and the prevalence increased with the risk of T21 by cFTS. In pregnancies with a risk of T21 > 1 in 100, a high risk of both T21 and T18, an increased NT, or a pregnancy-associated plasma A (PAPP-A) level < 0.2 multiple of medians (MoM), the prevalence of common abnormalities was 12.2, 64.7, 25.5 and 33.8%, respectively, while that of atypical abnormalities was 1.6, 3.9, 4.2, and 7.4%, respectively. In the multivariable binary logistic regression analysis, out of these four factors, only two (increased NT and PAPP_A < 0.2 MoM) were significant predictors of common and atypical abnormalities, respectively. Of all positive cFTS pregnancies, 50.4% did not have any of these four factors, and the prevalence of common and atypical abnormalities was 1.1 and 0.6%, respectively. There were three atypical abnormalities, all of which were mosaicism, and they were detected among women with IPD alone. The ages of these women were ≥ 35 years. All three pregnancies were continued after proper counseling. After giving birth, only one child had mild abnormalities, while the other two were phenotypically normal.ConclusionsOur study identified factors associated with common and atypical abnormalities after cFTS. These factors can be used to estimate the prior risk for these abnormalities to help with post-cFTS counseling in terms of choosing between cfDNA testing and IPD.

Risk of operative delivery for intrapartum fetal compromise in small-for-gestational-age fetuses at term: external validation of the IRIS algorithm

Objectives: Small-for-gestational-age fetuses (SGA) are at high risk of intrapartum fetal compromise requiring operative delivery. In a recent study, we developed a model using a combination of three antenatal (gestational age at delivery, parity, cerebroplacental ratio) and three intrapartum (epidural use, labor induction and augmentation using oxytocin) variables for the prediction of operative delivery due to presumed fetal compromise in SGA fetuses – the Individual RIsk aSsessment (IRIS) prediction model. The aim of this study was to test the predictive accuracy of the IRIS prediction model in an external cohort of singleton pregnancies complicated by SGA.Methods: This was an external validation study using a cohort of pregnancies from two tertiary referral centers in Spain and England. The inclusion criteria were singleton pregnancies diagnosed with an SGA fetus, defined as estimated fetal weight (EFW) below the 10th centile for gestational age at 36 weeks or beyond, which had fetal Doppler assessment and available data on their intrapartum care and pregnancy outcomes. The main outcome in this study was the operative delivery for presumed fetal compromise. External validation was performed using the coefficients obtained in the original development cohort. The predictive accuracies of models were investigated with receiver operating characteristics (ROC) curves. The Hosmer–Lemeshow test was used to test the goodness-of-fit of models and calibration plots were also obtained for visual assessment. A mobile application using the combined model algorithm was developed to facilitate clinical use.Results: Four hundred twelve singleton pregnancies with an antenatal diagnosis of SGA were included in the study. The operative delivery rate was 22.8% (n = 94). The group which required operative delivery for presumed fetal compromise had significantly fewer multiparous women (19.1 versus 47.8%, p < .001 in the total study population; 19.0 versus 43.5 and 19.2 versus 49.6%, UK and Spain cohort, respectively), lower cerebroplacental ratio (CPR) multiples of median (MoM) (median: 0.77 versus 0.92, p < .001 in the total study population; 0.77 versus 0.92 and 0.77 versus 0.92, UK and Spain cohort, respectively), more inductions of labor (74.5 versus 60.1%, p = .010 in the total study population; 85.7 versus 77.2 and 71.2% and 53.1, UK and Spain cohort, respectively) and more use of oxytocin augmentation (57.4 versus 39.3%, p = .002 in the total study population; 19.0 versus 12.0 and 68.5 and 50.4%, UK and Spain cohort, respectively) compared to those who did not require operative delivery due to presumed fetal compromise. When the original antenatal model was applied to the present cohort, we observed moderate predictive accuracy (AUC: 0.70, 95% CI: 0.64–0.76), and no signs of poor fit (p = .464). The original combined model, when applied to the external cohort, had moderate predictive accuracy (AUC: 0.72, 95% CI: 0.67–0.77) and also no signs of poor fit (p = .268) without the need for refitting. A statistically significant increase in the predictive accuracy was not achieved via refitting of the combined model (AUC 0.76 versus 0.72, p = .060).Conclusions: Using our recently published model, the predictive accuracy for fetal compromise requiring operative delivery in term fetuses thought to be SGA was modest and showed no signs of poor fit in an external cohort. The IRIS tool for mobile devices has been developed to facilitate wide clinical use of this prediction model.Brief rationaleObjective: To determine the external validity of an intrapartum risk prediction model for suspected small-for-gestational age fetuses.What is already known: Small-for-gestational age fetuses are at increased risk of intrapartum compromise. Fetal weight alone is a poor marker for adverse outcomes and a comprehensive prediction model has been previously suggested.What this study adds: Multivariable prediction model showed good accuracy and calibration in this external validation study. The significance of some variables was different between the original and external validation cohort and there was a small margin for improvement with model refitting. A mobile application has been developed to facilitate clinical use.

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study

Objective: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. Methods: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. Results: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. Conclusion: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

First-Trimester Uterine Artery Doppler for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndrome Study.

This study aimed to estimate the performance of first-trimester uterine artery (UtA) pulsatility index (PI) for the prediction of preeclampsia (PE). We conducted a prospective cohort study of nulliparous women with singleton gestation at 11 to 13 6/7 weeks. UtA-Doppler's was performed on both UtAs and the mean UtA-PI was reported in multiple of median (MoM) adjusted for gestational age. Using receiver operating characteristic curves and their area under the curves (AUC); we calculated the performance of UtA-PI for the prediction of PE. Proportional hazard models were used to develop prediction models combining UtA-PI and maternal characteristics. Out of 4,676 participants with completed follow-up, 232 (4.9%) developed PE, including 202 (4.3%) term and 30 (0.6%) preterm PE. Mean UtA-PI decreased with gestational age between 11 and 13 6/7 weeks (p < 0.001). First-trimester UtA-PI was associated with preterm (AUC: 0.69; 95% CI [confidence interval]: 0.57-0.80) but not with term (AUC: 0.52; 95% CI: 0.48-0.56) PE. UtA-PI combined with maternal characteristics could predict 45% of preterm PE at a false positive rate of 10%. First-trimester UtA-PI decreases with gestational age between 11 and 13 6/7 weeks and is associated with the risk of preterm but not term PE.

First-trimester serum biomarker screening for fetal Down syndrome as a predictor of preterm delivery: a population-based study

Objective: To examine the relationship between the first-trimester serum biomarker levels (pregnancy-associated plasma protein A:PAPP-A; and free beta-human chorionic gonadotropin: b-hCG) and preterm birth; and to create the predictive models for preterm birth in case of strong correlation. Methods: Secondary analysis on a large prospective database of singleton pregnancies undergoing first-trimester serum screening with complete follow-up for pregnancy outcomes. The multiples of medians (MoM) of the biomarkers were compared between the group of term and preterm/early preterm birth. Predictive models were developed based on adjusted MoMs and logistic regression analysis, and then diagnostic performances in predicting preterm birth were assessed. Results: Of 24,611 pregnancies eligible for analysis, 1908 (7.8%) and 500 (2.0%) had preterm and early preterm birth, respectively. Medians MoMs of both biomarkers were significantly lower in preterm and early preterm birth group. The predictive models were constructed. Performance in predicting preterm birth of these models yielded the area-under-ROC-curve of 0.560, 0.652, and 0.653 for b-hCG, PAPP-A, and combined biomarkers, respectively. In predicting early preterm birth, the areas-under-the-curve were found to be 0.551, 0.675, and 0.674 for b-hCG, PAPP-A, and combined biomarkers, respectively. Conclusion: The routine first-trimester serum screening of fetal Down syndrome could also be used as a tool of risk identification of preterm birth. We could take advantage of the screening by incorporating the predictive models into the Down syndrome screening software to report the preterm risk in the same test without extra effort and extra cost

QUANTITATIVE DETECTION OF CAMV- 35S PROMOTER AND T-NOS TERMINATOR IN GENETIC MODIFIED TOMATO FROM IRAQI MARKETS

Aim of this research was quantitative detection of Increase and decrease in copy number of CaMV-35S promoter and Nos terminator in genetic modified tomato by using Real-time PCR. Twenty four samples of genetic modified tomato seeds were isolated from 84 tomato samples collected from Iraqi markets during the period from December 2016 to January 2017. The experiences were conducted in the Institute of Genetic Engineering, University of Baghdad. Go Taq®qPCR master mix kit supplied by USA Promega Company, three specific primers to CaMV-35S promoter, T-Nos terminator and β-actin housekeeping gene supplied by Canadian Alpha Company were used. To quantitative detection of increase and decrease in copy number of GM tomato samples contain CaMV-35S promoter and T-Nos terminator, comparing with the β-actin (houskeeping gene) using Multiple of Median (MoM) equation. The results showed that the lowest recorded of Ct value was (27.88) for CaMV-35S promoter gave an increase in copy number (1.1766) above the normal limit, while highest recorded of Ct value was (32.67) gave an increase in copy number (1.0350) above the normal limit. The lowest recorded of Ct value was (27.35) for T-Nos terminator gave an increase in copy number (1.1600) above the normal limit, whereas highest recorded of Ct value was (32.82) gave a decrease in copy number (0.9920) under the normal limit.

First-Trimester Uterine Artery Doppler for the Prediction of SGA at Birth: The Great Obstetrical Syndromes Study

To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA). We conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11 + 0 to 13 + 6 weeks and was reported in multiple of median (MoM). SGA was defined as birth weight below the 10th percentile and stratified as term or preterm SGA. Receiver operating characteristic curves analyses with their area under the curve (AUC) were used to estimate the predictive values of UtA-PI, alone and UtA-PI combined with maternal characteristics. We computed the detection rate and false-positive rate (FPR) of the SOGC SGA screening guidelines in our population. Of 4610 participants, SGA was identified in 486 pregnancies (10.3%), including 15 (0.3%) associated with preterm delivery. Compared with unaffected pregnancies, the mean log UtA-PI was significantly higher in term SGA and preterm SGA. The difference between preterm SGA and unaffected pregnancies remains significant after exclusion of SGA without preeclampsia. First-trimester UtA-PI was more predictive of preterm (AUC: 0.89) than term (AUC: 0.60) SGA (P < 0.01). Combined with maternal characteristics, UtA-PI could have predicted 64% of preterm and 20% of term SGA (10% FPR). The SOGC guidelines criteria for early screening of SGA had a detection rate of 21% for a FPR of 21%. First-trimester UtA-PI can be used to predict SGA, but mainly preterm SGA. The current SOGC guidelines criteria for SGA screening are not efficient in nulliparous women.

Unexpected middle cerebral artery peak systolic velocity values in the normal fetal population. Are they a matter of concern?

Objective: The aim of this study was to investigate in the fetus the relationship between unexpected high middle cerebral artery peak systolic velocity (middle cerebral artery (MCA) peak systolic velocity (PSV)) values and hemoglobin (Hgb) levels in normal pregnancies without conditions leading to fetal anemia.Material and methods: This was a prospective study of 922 singleton low-risk pregnant women attending the maternity of La Fe Hospital between 35 and 41 weeks. Multiple pregnancies and pregnancies with growth restriction, smallness, macrosomia or conditions leading to fetal anemia were excluded. During each examination, a biometry and a Doppler examination of the umbilical artery pulsatility index (umbilical artery (UA) pulsatility index (PI)), MCA PI and MCA PSV were performed. MCA PSV was converted into multiples of median (MoM), and birth weight (BW) into centiles adjusting for gender. All pregnancies delivered in a 2-week interval since examination. In order to explain Hgb levels at birth, a correlation between MCA PSV MoM and Hgb was performed and Hgb levels of fetuses with normal MCA PSV and abnormal MCA PSV were compared, using 1.3 MoM as cut-off for mild anemia. Finally, a multivariate linear regression analysis was performed including MCA PSV MoM and several Doppler and clinical parameters.Results: The univariate analysis showed no correlation between the MCA PSV MoM and the umbilical artery Hgb (r2 = 0.026, p = .1237) while a weak correlation was found with the umbilical vein Hgb (r2 = 0.0053, p = .027). Also, fetuses with values of MCA PSV MoM <1.3 MoM did not differ in terms of artery and vein Hgb with those presenting values >1.3 MoM (p = .99 and p = .61, respectively). Finally, both prediction models explaining arterial and venous Hgb presented very weak predictive accuracies (R Squared: 0.0965 and R Squared: 0.106) indicating a low possibility to diagnose fetal anemia in otherwise normal fetuses based on clinical and sonographic data.Conclusion: In normal pregnancies that are not suffering from conditions leading to fetal anemia, unexpected high MCA PSV values do not necessarily reflect the presence of this condition. Active management in this circumstance might result in unjustified higher rates of labor induction and operative delivery.

A disintegrin and metalloproteinase domain-containing protein-12 levels in first-trimester pregnant women

Aim: In this prospective monocenter study, the authors aimed to investigate the correlations between levels of serum human disintegrin and metalloproteinase domain-containing protein 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), serum-free beta hCG (f&#x03B2;-hCG), and baby birth weights in two groups of pregnant women whose risks for trisomy 21 was found higher and lower than threshold value in first trimester screening test. Materials and Methods: Seventy-nine pregnant women were included the study. Using first trimester screening test, 40 of them were categorized as having above threshold risk (1/250) for trisomy 21 and, 39 of them were below threshold risk. ELISA method was used to measure the levels of serum ADAM12 and chemiluminescence method was used to measure the levels of PAPP-A and f&#x03B2;-hCG. Results: In pregnant women at risk, ADAM12, PAPP-A multiple of median (MoM), and baby birth weights were found significantly lower than control group (p p p = 0.029, respectively) while the levels of f&#x03B2;-hCG MoM were higher than those of control group (p p p r = 0.630). Conclusions: Maternal serum ADAM12 levels are useful as biomarkers which support other screening parameters for predicting trisomy 21 risk. Additionally, maternal serum ADAM12 levels could be used for prediction of baby birth weights.

Optimization of regional median equations of prenatal screening markers for trisomy 21 in a Chinese population.

To establish gestational age-specific and body weight-specific mid-trimester normal median equations for the prenatal serum markers α-fetoprotein (AFP), free β subunit human chorionic gonadotropin (fβHCG), and unconjugated oestriol (uE3) for a Chinese population; to compare and replace the median equations built in LifeCycle software; to evaluate the effect of equations used for gestation correction on estimating risk in Down's syndrome, Edward's syndrome, and neural tube defect (NTD).A total of 353,065 cases of prenatal screening data of pregnant women were screened by 13 prenatal screening institutions in China. The local median equations of each institution and the large data were fitted by the least square regression, and then the difference was compared between large data equations and local median equations. The applicability of the localized median equations was evaluated by the determination coefficient. Based on the established median equations, multiples of median (MoM) of each values were calculated and compared with the latest Down's syndrome quality assurance support service (DQASS).There is no significant difference between the local median equations of each institution and the large sample median equations, which are various from LifeCycle built-in median equations. Besides, the determination coefficient of localized median equations are >0.99. 97.0% MoM medians obtained by using local median equations are consistent with latest standard of DQASS.The median established by large sample data represents the median level of a Chinese population, and can be used to replace the software built-in median equations to achieve better screening results.

Cell-Free DNA (cfDNA) Fetal Fraction in Early- and Late-Onset Fetal Growth Restriction.

Our objective was to retrospectively evaluate whether the levels of cell-free DNA (cfDNA) fetal fraction differed in the first trimester of pregnancies between controls and those who subsequently developed early- or late-onset fetal growth restriction (FGR). This was a case-control study conducted between May 2015 and May 2018 in 231 low-risk women who had received first trimester screening for major fetal aneuploidies (Panorama, Natera, San Carlos, CA, USA). Early- and late-onset FGR developed in 5 and 16 women, respectively, according to Delphi criteria. Multiples of median (MoM) were used to evaluate the differences in cfDNA fetal fraction between cases and controls. cfDNA fetal fraction was adjusted for gestational age (from 10 + 0 to 13 + 6 gestational weeks) and maternal weight (43-96kg). The median cfDNA fetal fractions for controls and early- and late-onset FGR were 1.00 (interquartile range [IQR] 0.89-1.12), 0.69 (IQR 0.44-0.84) and 0.93 (IQR 0.83-1.03) MoM, respectively. Statistically lower cfDNA fetal fraction MoM values were observed onlyin patients with early-onset FGR (Kruskal-Wallis test with Dunn post hoc test). In a 1:35 ratio (one case of early-onset FGR: 35 controls), the mean observed rank of 2.00 ± 2.23 in the cases was significantly lower than the expected 18.97 ± 10.17 (p < 0.001). Low-risk pregnancies that developed early-onset FGR had lower cfDNA fetal fractions than did the matched controls. This result is consistent with the placental dysfunction typical of early-onset FGR. For possible clinical use, the cfDNA fetal fraction would yield a better predictive value if adjusted for maternal weight, since maternal weight affects both cfDNA fetal fraction and the occurrence of FGR.

First trimester prenatal screening biomarkers and gestational diabetes mellitus: A systematic review and meta-analysis.

Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first trimester measurements of prenatal screening biomarkers are associated with subsequent risk of gestational diabetes mellitus (GDM). We aimed to systematically review and statistically summarize studies assessing the relationship between first trimester prenatal screening biomarker levels and GDM development. We comprehensively searched PubMed/MEDLINE, EMBASE, CINAHL, and Scopus (from inception through January 2018) and manually searched the reference lists of all relevant articles. We included original, published, observational studies examining the association of first trimester pregnancy associated plasma protein-A (PAPP-A) and/or free β-human chorionic gonadotropin (free β-hCG) levels with GDM diagnosis. Mean differences were calculated comparing PAPP-A and free β-hCG multiples of median (MoM) levels between women who developed GDM and those who did not and were subsequently pooled using two-sided random-effects models. Our meta-analysis of 13 studies on PAPP-A and nine studies on free β-hCG indicated that first trimester MoM levels for both biomarkers were lower in women who later developed GDM compared to women who remained normoglycemic throughout pregnancy (MD -0.17; 95% CI -0.24, -0.10; MD -0.04; 95% CI -0.07–0.01). There was no evidence for between-study heterogeneity among studies on free β-hCG (I2 = 0%). A high level of between-study heterogeneity was detected among the studies reporting on PAPP-A (I2 = 90%), but was reduced after stratifying by geographic location, biomarker assay method, and timing of GDM diagnosis. Our meta-analysis indicates that women who are diagnosed with GDM have lower first trimester levels of both PAPP-A and free β-hCG than women who remain normoglycemic throughout pregnancy. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed.

Multiples of Median-Transformed, Normalized Reference Ranges of Steroid Profiling Data Independent of Age, Sex, and Units

Background/Aims: The high complexity of pediatric reference ranges across age, sex, and units impairs clinical application and comparability of steroid hormone data, e.g., in congenital adrenal hyperplasia (CAH). We developed a multiples-of-median (MoM) normalization tool to overcome this major drawback in pediatric endocrinology. Methods: Liquid chromatography tandem mass spectrometry data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to > 16 years) from 2 previous datasets were MoM transformed across age and sex. Twenty-three genetically proven CAH patients were included (21-hydroxylase deficiency [21OHD], n = 19; 11β-hydroxylase deficiency [11OHD], n = 4). MoM cutoffs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, n = 8; adrenal cortical carcinoma, n = 6; obesity, n = 40). Results: 21OHD and 11OHD patients showed disease-typical, easily recognizable MoM patterns independent of age, sex, and concentration units. Two single-steroid cutoffs indicated 21OHD: 3.87 MoM for 17-hydroxyprogesterone (100% sensitivity and 98.83% specificity) and 12.28 MoM for 21-deoxycortisol (94.74% sensitivity and 100% specificity). A cutoff of 13.18 MoM for 11-deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity). Conclusions: Age- and sex-independent MoMs are straightforward for a clinically relevant display of multi-steroid patterns. In addition, defined single-steroid MoMs can serve alone as predictors of 21OHD and 11OHD. Finally, MoM transformation offers substantial enhancement of routine and scientific steroid hormone data exchange due to improved comparability.

First trimester combined screening biochemistry in detection of congenital heart defects

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs).Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down’s syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland.Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively.Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.