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Objectives. The evaluation of maternal biomarkers that can guide us towards an early diagnosis of gestational diabetes, as early as the first trimester of pregnancy, for a better management and to reduce potential adverse effects of gestational diabetes on pregnancy and pregnant women. Methodology. This article reviews research in the specialized literature and aims to highlight how biomarkers, such as fasting glucose, HOMA score, glycated hemoglobin and PAPP-A, can constitute a set of parameters for screening gestational diabetes as early as the first trimester of pregnancy. Results. Women who developed gestational diabetes exhibited higher values of biomarkers compared to patients unaffected by this metabolic imbalance. Diagnosing gestational diabetes in the first trimester of pregnancy requires correlating multiple biological markers. Most studies suggest that none of the markers used alone have a sufficiently high predictive value for screening gestational diabetes in the first trimester. However, their correlation can quantify the risk of developing this condition and provide a clinical clue in routine practice. [ABSTRACT FROM AUTHOR]

Early recognition of high-risk pregnancies through biochemical markers may promote antenatal surveillance, resulting in improved pregnancy outcomes. The goal of this study is to evaluate the possibilities of using biochemical markers during the first trimester of pregnancy in the prediction of hypertensive pregnancy disorders (HPD) and the delivery of small-for-gestational-age (SGA) neonates. A comprehensive search was conducted on key databases, including PubMed, Scopus, and Web of Science, for articles relating to the use of biochemical markers in the prediction of HPD and SGA. The findings show that changes in the levels of biomarkers in the early pregnancy phases could be an important indicator of adverse pregnancy outcomes. The literature shows that low PAPP-A (pregnancy-associated plasma protein A) and PlGF (placental growth factor) levels, low alkaline phosphatase (AP), higher sFlt-1 (soluble fms-like Tyrosine Kinase-1) levels, higher AFP (alfa fetoprotein) levels, and elevated levels of inflammatory markers such as β-HGC (free beta human chorionic gonadotropin), interferon-gamma (INF-γ), and tumor necrosis factor-α (TNF-α) may be associated with risks including the onset of HPD, fetal growth restriction (FGR), and delivery of SGA neonates. Comparatively, PAPP-A and PlGF appear to be the most important biochemical markers for the prediction of SGA and HPD. [ABSTRACT FROM AUTHOR]

Copyright of Ahi Evran Medical Journal is the property of Ahi Evran University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to investigate the potential of pregnancy-associated plasma protein A (PAPP-A) and clinical data in predicting gestational diabetes mellitus (GDM). Clinical data of 318 pregnant women with GDM and 200 healthy pregnant women were retrospectively analysed. The age, BMI and caesarean section in GDM were significantly higher than in normal group. Serum and placental levels of PAPP-A were significantly lower in GDM than in normal group. Pearson's correlation analysis showed that serum levels of PAPP-A were negatively correlated with BMI and blood glucose level. Binary logistic regression analysis displayed that PAPP-A were the potential factors influencing GDM. The area under the ROC curve (AUC) for PAPP-A combined with BMI in predicting GDM was 0.941, significantly higher than that of the single one. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. What is already known on this subject? GDM not only increases the risk of perinatal morbidity, but also results in an increased risk of long-term sequelae for both mother and child including diabetes, cardiovascular disease obesity. Previous data indicate that besides glycemic control in the second trimester, interventions initiated early in pregnancy can reduce the rate of GDM in pregnant women. The expression of PAPP-A in serum of GDM pregnant women was decreased in the first trimester. Whereas, whether PAPP-A can be as an early predictor of GDM is not clear. What do the results of this study add? The present study shows that PAPP-A MoM was less than 0.6757 in the first trimester of pregnancy is more prone to GDM. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. What are the implications of these findings for clinical practice and/or further research? Early GDM prediction is crucial for prevention and management of GDM, to cope with the rising prevalence of GDM and reduce later life chronic disease of both mother and child. Based on the level of PAPP-A MoM and BMI, interventions such as lifestyle changes initiated early in pregnancy shouldbeenabledin pregnant women. [ABSTRACT FROM AUTHOR]

Copyright of Medical Journal of Istanbul Kanuni Sultan Süleyman / İstanbul Kanuni Sultan Süleyman Tıp Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The present study was designed to evaluate and compare the screening markers of spontaneous and in vitro fertilization (IVF) pregnancies in individuals who underwent combined screening in the first trimester of pregnancy. Materials and Methods: In this retrospective study, we examined the difference between natural and assisted-reproductive technology (ART) pregnancies in 2252 mothers from January 2011 to October 2019. In both groups, the first trimester screening parameters including NT, free beta-human chorionic gonadotropin (ß-hCG), and PAPP-A were measured. Results: According to the results of the present study, BMI was higher in the group that became pregnant by IVF compared to the normal pregnancy group (P < 0.001). Additionally, in patients using IVF, the history of maternal disease was less frequent compared to the other group (P = 0.003). Most cases of twin fetuses, dichorionic twin pregnancy, and fetal abnormality were seen in the IVF group. Although the ß-hCG and free PAPP-A levels were high in the IVF group, no significant difference was observed. The group with spontaneous pregnancy had a higher penetration rate of nuchal translucency <95th percentile compared to the IVF group (P < 0.001). The results of comparing the first trimester test showed that in the IVF group, 81.3% of patients were at low risk and 6.6% were at high risk, while in the normal pregnancy group, 78.9% of patients were at low risk and 7.0% of them were at low risk, indicating that the difference was not significant. Conclusions: Overall, although the risk of aneuploidy in IVF pregnancies was not higher compared to normal pregnancies, in IVF pregnancies, NI is associated with a high risk of fetal abnormalities. Therefore, NT sonography can help to diagnose fetal anomalies especially aneuploidy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of using progesterone due to early vaginal bleeding on aneuploidy screening markers in the first trimester.Material and Methods: This case control study includes the pregnant women who applied to our clinic in order to have a screening test for Down syndrome in the weeks of 11°/7-136/7. The patients were divided into three groups. Self reported vaginal bleeding with progesterone therapy (Bl+, Prg+, n:70), Self reported vaginal bleeding without progesterone therapy (Bl+, Prg-, n:70) and as a control group pregnant women who had no vaginal bleeding. (NoBl, NoPrg, n:70). In all patients, free beta-human chorionic gonadotrophin (β-hCG), pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency (NT) thickness were analyzed. Mean MoMs of the markers were compared between three groups.Results: In the two groups with vaginal bleeding (Bl+, Prg + and Bl+, Prg-) the free β-Hcg MoM values were statistically higher (1.22 ± 0.72, 0.98 ± 0.45, respectively) compared to the No Bleeding/No Progesterone group (0.81 ± 0.52) (p ≤ 0.001, p ≤ .01, respectively). However, no significant difference was found between the free β-hCG MoM value of women with Bl+, Prg + group (1.22 ± 0.72) and Bl+, Prg - group (0.98 ± 0.45). (p: .053, significance level limitation with Bonferroni correction p: .017). PAPP-A and NT thickness did not differ significantly between the groups.Conclusion: Our data did not find an association between the use of oral progesterone and any alternations in first trimester screening parameters. Regardless of the progesterone usage, vaginal bleeding in the first trimester pregnancies increased the free β-hCG MoM values compared to pregnancies without vaginal bleeding during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome.Methods: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA).Results: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile.Conclusions: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Abstract Background Preeclampsia (PE) is a leading cause of maternal and perinatal mortality. There are controversial findings regarding the prediction of PE through the assessment of the Pregnancy-Associated Plasma Protein A (PAPP-A) and β-Human-Derived Chorionic Gonadotrophic hormone (βhCG) levels in the first trimester of pregnancy. Therefore, this cohort study was conducted to evaluate of PAPP-A and βhCG levels as predictive factors for PE development in the first trimester among Iranian women. Methods In this cohort study, a total of 4605 volunteer Primigravida and Multigravida women were selected by the census from 16 randomly selected Health Centers in Isfahan, Iran, from July 2016 to June 2018. Eligible pregnant women participated in the study had already undergone fetal anomalies screening tests between 11 + 0 and 13 + 6 weeks of pregnancy and their PAPP-A and βhCG biomarkers were adjusted to the Multiples of the Median (MOM). MOM PAPP-A 3 were considered abnormal. The samples were followed up until delivery. The biomarkers’ levels were compared in the two groups of women with and without PE and Relative risk (RR) and odds ratio (OR) of PE calculated. Results In the PE group, the mean MOM PAPP-A was significantly lower (1 vs. 1.09 with P = 0.006) and MOM βhCG was significantly higher (1.51 vs. 1.14 with P = 0.001) than the group without PE. RR and OR for PE in subjects with MOM PAPP-A 3 were also reported as follows: RR = 4.02, (p = 0.001) and OR = 5.65, (p = 0.001). Adjusted OR for MOM PAPP-A 3 was obtained as follows: OR = 2.09 (P = 0.001) and OR = 5.65 (P = 0.001), respectively. Conclusion The results of the study showed that the high levels of βhCG would cause 5.65 times increase and the low levels of PAPP-A would cause 2.09 times increase in the chance of developing PE.

Aims: To compare the screening capability of ultrasonography in detecting trisomy 13 (T13) using a multiparameter sonographic protocol (NT+) with a classical combined screening test (CST) protocol.Methods: The project was a prospective, multicenter study based on a nonselected mixed-risk population of women referred for a first-trimester screening examination. Each subject was offered a choice between either the gold standard, traditional combined screening test (CSG arm) or the ultrasound-based screening protocol (USG arm). General and MA-based screening performances were checked.Results: The study population comprised 20,887 pregnancies: 12,933 in the CSG arm, including 27 cases of T13, and 7954 in the USG arm, including 30 cases of T13. The DR for T13 was higher in the CSG arm than in the USG arm for all tested cutoff points: 1/50 (88.5 versus 63.3%, respectively), 1/100 (88.5 versus 70%, respectively) and 1/300 (92.3 versus 83.3%, respectively). Using the ROC curves for fixed FPRs of 3 and 5%, the T13 detection rate in our study reached 90 and 93%, respectively, in the USG arm and 92 and 96%, respectively, in the CSG arm. MA influenced the T13 screening performance in the USG arm and reduced the DR in patients <31 years. Such influence was not detected in the CSG arm.Conclusions: Classic CST was more effective in detecting T13 than the ultrasound-only approach. However, the recommended cutoff of 1/50 showed unsatisfactory results for both traditional CST and the multiparameter sonographic test we proposed. [ABSTRACT FROM AUTHOR]

Purpose: To develop a first trimester prediction model for gestational diabetes mellitus (GDM) using obesity, placental, and inflammatory biomarkers.Methods: We used a first trimester dataset of the ASPRE study to evaluate clinical and biochemical biomarkers. All biomarkers levels (except insulin) were transformed to gestational week-specific medians (MoMs), adjusted for maternal body mass index (BMI), maternal age, and parity. The MoM values of each biomarker in the GDM and normal groups were compared and used for the development of a prediction model assessed by area under the curve (AUC).Results: The study included 185 normal and 20 GDM cases. In the GDM group, compared to the normal group BMI and insulin (P = 0.003) were higher (both P < 0.003). The MoM values of uterine artery pulsatility index (UtA-PI) and soluble (s)CD163 were higher (both P < 0.01) while pregnancy associated plasma protein A (PAPP-A), placental protein 13 (PP13), and tumor-necrosis factor alpha (TNFα) were lower (all P < 0.005). There was no significant difference between the groups in placental growth factor, interleukin 6, leptin, peptide YY, or soluble mannose receptor (sMR/CD206). In screening for GDM in obese women the combination of high BMI, insulin, sCD163, and TNFα yielded an AUC of 0.95, with detection rate of 89% at 10% false positive rate (FPR). In non-obese women, the combination of sCD163, TNFα, PP13 and PAPP-A yielded an AUC of 0.94 with detection rate of 83% at 10% FPR.Conclusion: A new model for first trimester prediction of the risk to develop GDM was developed that warrants further validation. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to determine the relationship between hyperemesis gravidarum and maternal serum pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG) levels. This study was designed as a case-control study. Methods: The study group consists of 54 pregnant women of 10-14 weeks who were diagnosed with hyperemesis gravidarum in the İstanbul Training and Research Hospital Hospital while the control group consists of 54 pregnant women of 10-14 weeks who did not have any complaints. Thyroid stimulating hormone, free T3, free T4, aspartate aminotransferase, alanine aminotransferase, PAPP-A, and hCG values and age were retrospectively scanned from files. Results: We have observed that the hyperemesis gravidarum group has higher hCG levels as compared with the control group. The mean hCG level in control group and hyperemesis group was 1.10±0.569 and 1.55±1.140, respectively (p<0.05) The mean PAPP-A level in control group and hyperemesis group was 1.00±0.611, 1.36±0.887, respectively (p<0.05). Conclusion: Elevated levels of PAPP-A and hCG are associated with hyperemesis gravidarum. More comprehensive studies are needed to explain the role of PAPP-A in the pathogenesis of hyperemesis gravidarum. [ABSTRACT FROM AUTHOR]

Objective: Serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 11-13 weeks' gestation are reduced in pregnancies with fetal trisomy and in those that subsequently develop pre-eclampsia (PE). In screening for trisomy, the established biochemical marker is PAPP-A, whereas in screening for PE, the preferred marker is PlGF. The objective of this study was to examine the impact of replacing PAPP-A by PlGF in first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency thickness (NT) and free β-human chorionic gonadotropin (β-hCG).Methods: This was a prospective screening study in singleton pregnancies for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT and serum PAPP-A and free β-hCG at 11-13 weeks' gestation in which we also measured PlGF. Multiples of the median (MoM) values were calculated for PAPP-A, free β-hCG and PlGF. The dataset was split randomly into training and test datasets of roughly equal size, and the parameters for PlGF obtained from the training dataset were used in risk calculation for the test dataset. Standardized detection rates were computed by obtaining the likelihood ratios for biochemistry and fetal NT for trisomy-21, -18 and -13 pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific detection rates. These were then weighted according to the maternal age distributions of trisomy-21, -18 and -13 pregnancies in England and Wales in 2018. Similarly, standardized false-positive rates (FPR) were computed by obtaining the likelihood ratios for biochemistry and NT, as appropriate, in normal pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific FPRs. A modeling approach was used to assess the performance of screening according to gestational age at biochemical testing.Results: The study population of 71 266 pregnancies included 70 858 (99.4%) with normal fetal karyotype or birth of a phenotypically normal neonate and 263 with trisomy 21, 109 with trisomy 18 and 36 with trisomy 13. There are five main findings of this study. First, the performance of screening for trisomy by the first-trimester combined test or the combined test in which PAPP-A is replaced by PlGF is substantially better at 11 than at 13 weeks' gestation; for example, the detection rates of trisomy 21 by the combined test were 94%, 90% and 84%, at 5% FPR, when testing was carried out at 11, 12 and 13 weeks, respectively, and the corresponding values in screening by a test in which PAPP-A is replaced by PlGF were 90%, 87% and 86%, respectively. Second, in trisomy-21 pregnancies, the deviation of median PAPP-A MoM from normal decreases with increasing gestational age, whereas the deviation in PlGF does not change with gestational age. Third, the performance of screening for trisomy 21 during the 11th and 12th gestational weeks is superior if screening includes PAPP-A rather than PlGF, whereas during the 13th week the performance is slightly higher with the use of PlGF rather than PAPP-A. Fourth, in our population with mean gestational age at testing of 12.7 weeks, screening by maternal age, fetal NT, serum free β-hCG and serum PAPP-A predicted 88%, 96% and 97% of cases of fetal trisomies 21, 18 and 13, respectively, at a FPR of 5%; the respective values in screening by a test in which PAPP-A is replaced by PlGF were 85%, 96% and 96%. Fifth, addition of serum PlGF does not improve the prediction of trisomy provided by maternal age, fetal NT and serum free β-hCG and PAPP-A.Conclusion: In first-trimester screening for trisomy, the preferred biochemical marker is PAPP-A rather than PlGF, especially when biochemical testing is carried out during the 11th week of gestation or earlier. However, if PlGF was to be used rather than PAPP-A, the same detection rate can be achieved but at a higher FPR. This may be an acceptable compromise to minimize cost and achieve effective screening for both trisomy and PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: First-trimester screening for pre-eclampsia (PE) is useful because treatment of the high-risk group with aspirin reduces the rate of early PE with delivery at < 34 weeks' gestation by about 80% and that of preterm PE with delivery at < 37 weeks by 60%. In previous studies, we reported that the best way of identifying the high-risk group is by a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). An alternative biochemical marker is pregnancy-associated plasma protein-A (PAPP-A), which is used widely as part of early screening for trisomy. The objective of this study was to examine the additive value of PlGF and PAPP-A in first-trimester screening for preterm PE by maternal factors, MAP and UtA-PI and define the risk cut-off and screen-positive rate to achieve a desired detection rate of PE if PAPP-A rather than PlGF was to be used for first-trimester screening.Methods: This was a non-intervention screening study. The data were derived from prospective screening for adverse obstetric outcomes in women with singleton pregnancy attending for a routine first-trimester hospital visit. Patient-specific risks of delivery with PE at < 37 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median (MoM) values of MAP, UtA-PI, PlGF and PAPP-A. The performance of screening in the total population and in subgroups of women of white and black racial origin was estimated. McNemar's test was used to compare the detection rate, for a fixed screen-positive rate, of screening with and without PlGF and PAPP-A. Risk cut-offs and screen-positive rates to achieve desired detection rates of preterm PE were determined in screening with and without PlGF and PAPP-A.Results: The study population was composed of 60 875 singleton pregnancies, including 1736 (2.9%) that developed PE. There are three main findings of this study. First, the performance of first-trimester screening for PE by a combination of maternal factors, MAP, UtA-PI and PlGF is superior to that of screening by maternal factors, MAP, UtA-PI and PAPP-A; for example, in screening by maternal factors, MAP, UtA-PI and PlGF, at a screen-positive rate of 10%, the detection rate of PE with delivery at < 37 weeks' gestation was 74.1%, which was 7.1% (95% CI, 3.8-10.6%) higher than in screening by maternal factors, MAP, UtA-PI and PAPP-A. Second, addition of serum PAPP-A does not improve the prediction of PE provided by maternal factors, MAP, UtA-PI and PlGF. Third, the risk cut-off and screen-positive rate to achieve a given fixed detection rate of preterm PE vary according to the racial composition of the study population and whether the biomarkers used for screening are MAP, UtA-PI and PlGF or MAP, UtA-PI and PAPP-A. For example, in screening by a combination of maternal factors, MAP, UtA-PI and PlGF in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 136 and the screen-positive rate would be 14.1%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 29 and the screen-positive rate would be 12.5%. In screening by a combination of maternal factors, MAP, UtA-PI and PAPP-A in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 140 and the screen-positive rate would be 16.9%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 44 and the screen-positive rate would be 19.3%.Conclusion: In first-trimester screening for PE, the preferred biochemical marker is PlGF rather than PAPP-A. However, if PAPP-A was to be used rather than PlGF, the same detection rate can be achieved but at a higher screen-positive rate. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy-associated plasma protein A (PAPP-A) protease is known for its role as a key regulator of insulin-like growth factors and hence of foetal development. With the present study we intend to investigate its role in the maternal haemodynamic adaptation to the state of pregnancy. Material and methods: We selected 18 patients referred to our unit between February 2017 and July 2017, of whom 10 showed low PAPP-A values at the first trimester screening for chromosomal anomalies. Each patient had 3 serial echocardiographic evaluations at the 13th, 24th, and 33rd week of pregnancy. On the basis of the plasma values of PAPP-A, the patients were divided into cases (n = 10) and controls (n = 8), where cases had a mean PAPP-A concentration of 0.345 with a standard deviation of 0.086, while the controls were characterised by a mean PAPPA concentration of 1.380 with a standard deviation of 0.613. The main outcome measures were peripheral vascular resistance (PVR), cardiac output (CO), systolic excursion of the tricuspid ring (TAPSE), and E/E’ ratio. Systolic and diastolic arterial blood pressure and heart rate (HR) were measured at each visit. Mono- and bidimensional, Doppler, and TDI images were acquired and analysed blindly by a single sonographer. Results: A slight increase in heart rate (HR, + 12%, p < 0.05) was observed in the control group at the 33rd week visit, while there was no change in the group with low levels of PAPP-A. Cardiac output and PVR also changed in the high-value PAPP-A group (ANOVA for repeated measures, p < 0.05), while they remained unchanged in the group with low PAPP-A values. It was observed that in the case group, the lower the PAPP-A values, the lower the extent of the haemodynamic adjustment in terms of PVR drop and increase in CO. A lack of physiological adaptation to pregnancy was also observed in the systolic function of the right ventricle. Women with normal PAPP-A showed a slight reduction (t test, p < 0.05) of TAPSE, while in women with low PAPP-A no change was observed. The E/E’ ratio was significantly increased in the control group at the last two visits (p < 0.005 and p < 0.05, respectively). Conclusions: This study shows that the physiological haemodynamic adaptation and the morphofunctional changes in the heart are incomplete in women with low PAPP-A levels, creating a favourable substrate for the development of preeclampsia. The assay of PAPP-A in the first trimester can therefore be used as a screening method to select at-risk pregnancies, with the aim of creating a specific path and a closer follow-up. [ABSTRACT FROM AUTHOR]

Background: The Fetal Medicine Foundation developed a multiple logistic regression algorithm for risk prediction of delivering a small for gestational age neonate. Aim: To validate this algorithm in an Australian population. Methods: At the combined first trimester screen participants' medical histories, demographic data, mean arterial pressure, uterine artery pulsatility index and pregnancy‐associated plasma protein‐A were assessed. After delivery, risk of delivering a small for gestational age neonate at <37 or ≥37 weeks gestation was retrospectively calculated using the Fetal Medicine Foundation algorithm. Results: Three thousand and eight women underwent prediction of risk for delivering a small for gestational age neonate. The algorithm detected 15.0% (95% CI: 3.2–37.9) of small for gestational age neonates delivered <37 weeks gestation at a fixed 10% false positive rate (or 35.0% (95% CI: 15.4–59.2) at a fixed 20% false positive rate). It detected 23.4% (95% CI: 16.1–30.7) of small for gestational age neonates delivered ≥37 weeks gestation at a fixed 10% false positive rate (or 39.1% (95% CI: 30.7–47.5) at a fixed 20% false positive rate). The algorithm performed significantly better than individual parameters (P < 0.05). The area under the receiver operating characteristic curve was 0.68 (95% CI: 0.56–0.80) and 0.70 (95% CI: 0.65–0.74) for small for gestational age neonates at <37 and ≥37 weeks gestation, respectively. Conclusions: The Fetal Medicine Foundation algorithm for first trimester prediction of small for gestational age neonates does not perform as well in an Australian population as in the original United Kingdom cohort. However, it performs significantly better than any individual test parameter in both preterm and term neonates. Incorporation of further variables may help improve screening efficacy. [ABSTRACT FROM AUTHOR]

Objective  To determine if patients with a history of low pregnancy-associated plasma protein A (PAPP-A) in an initial pregnancy are at higher risk for adverse obstetric outcomes in a subsequent pregnancy. Study Design  This was a retrospective cohort study in patients who underwent first trimester screening for PAPP-A in two consecutive pregnancies. Two groups were examined: patients who had low PAPP-A in the first pregnancy followed by normal PAPP-A in the second pregnancy and patients who had recurrent low PAPP-A. Maternal and neonatal outcomes were compared between the groups, with the primary outcome being intrauterine growth restriction (IUGR) or preeclampsia. Results  A total of 124 patients were included, representing 248 pregnancies. Ninety-two (74.2%) patients had normal PAPP-A in the second pregnancy, and 32 (12.9%) patients had recurrent low PAPP-A. Patients with recurrent low PAPP-A had a higher rate of IUGR or preeclampsia compared with patients with normal PAPP-A in the second pregnancy but this was not significantly different (12.5 vs. 10.9%, p  = 0.51). There were no significant differences for all other outcomes. Conclusion  Among patients with a history of low PAPP-A, patients with normal PAPP-A in the subsequent pregnancy have a similar risk of adverse neonatal outcomes compared with patients with recurrent low PAPP-A. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine if the levels of biochemical aneuploidy markers in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations. Methods: This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM). Results: The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%). Conclusions: The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications. [ABSTRACT FROM AUTHOR]

Objective To assess whether the accuracy of risk estimation in antenatal screening for trisomy 18 using the Combined test can be improved by revising the truncation limits of two serum markers. Methods In an audit of data from 420 trisomy 18 and 573,754 unaffected singleton pregnancies screened at the Wolfson Institute of Preventive Medicine, London (March 2003 to June 2017), the accuracy of risk estimation was assessed by inspection of a validation plot (the median predicted late first trimester Combined test risk plotted against observed prevalence within categories of predicted risk estimates). Using validation and probability plots, we assessed whether the revised pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (free β-hCG) truncation limits led to more accurate risk estimation and improved screening performance. Results With the lower truncation limits currently used for PAPP-A and free β-hCG (0.15 and 0.30 multiples of the median [MoM], respectively), risk was underestimated. Revised lower truncation limits of 0.05 MoM for both PAPP-A and free β-hCG led to greater accuracy, with an increase in the number of trisomy 18 pregnancies detected (from 85.4% to 90.2%) for a small increase in the false-positive rate (from 0.20% to 0.29%) at a 1 in 100 late first trimester risk cut-off. Conclusion The revised truncation limits for PAPP-A and free β-hCG increase the accuracy of trisomy 18 risk estimation and improve screening performance using the Combined test. Validation and probability plots are useful in setting screening marker truncation limits. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) MoM values and placenta accreta in women who had placenta previa.Study Design: A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fβhCG MoM values were compared in two groups with and without placenta accreta.Results: Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p = 0.045) and fβhCG MoM (1.42 versus 0.93, respectively, p = 0.042) values than patients without accreta.Conclusions: Higher first trimester serum PAPP-A and fβhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between maternal serum levels of pregnancy-associated-plasmaprotein- A (PAPP-A) and β-human-chorionic-gonadotropin (β-hCG) and pregnancy complications. Materials and methods: This is a case-control study conducted during 2015- 2016. Women at their first pregnancy were enrolled and serum PAPP-A and free-β-hCG were measured in 9-14 weeks of gestation. They were followed till the end of pregnancylooking for complications including preterm labor, pregnancy induced hypertension (PIH), abortion, and intra-uterine growth retardation (IUGR). Results: A total of 1070 pregnant women (mean age: 28.64 ± 4.95 years) were enrolled. Low serum levels of PAPP-A were more frequent in patients developing IUGR (17.4% versus 1.2%, p < 0.001), preterm labor (13% versus 2%, p = 0.013), and PIH (17.4% versus 4%, p = 0.015) compared those without complications. The serum levels of free-β-hCG were not different in patients with and without complications (p > 0.05). Conclusion: There is an association between low serum levels of PAPP-A and developing IUGR, preterm labor, and PIH. [ABSTRACT FROM AUTHOR]

Elevated levels of nausea and vomiting in pregnancy (NVP) and disgust sensitivity have been observed in the first trimester and both are thought to have a protective function for the mother and her fetus. Their aetiology is not clear, however, with previous studies attributing elevated NVP and disgust to various factors including endocrine changes, immunological changes, and psychological variables. To date, no study has directly assessed the relationship between disgust and NVP. Here, we prospectively collected two independent samples (S1 and S2; n 1 = 201, n 2 = 391) of women in the first trimester of pregnancy, who completed the Index of Nausea, Vomiting, and Retching and the Disgust Scale-Revised. We also measured free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Our results did not confirm any association between NVP and disgust; in addition, they indicate that NVP and disgust may have different proximate causes. Disgust sensitivity was significantly negatively correlated with free β-hCG and (only in S1) with PAPP-A. In contrast, NVP was significantly positively associated with free β-hCG levels and (only in S1) with PAPP-A. While low hCG levels seem to be an important indicator for activation of the behavioral immune system in the first trimester, increased hCG levels play a role in stronger symptoms of NVP, a result consistent with previous studies. Levels of PAPP-A are likely part of a larger network of immunological and endocrine responses and do not appear to provide sufficient information for predicting women's NVP and disgust sensitivity. • We studied nausea and vomiting in pregnancy (NVP) and disgust sensitivity (DS) levels. • Unexpectedly, NVP and DS were not significantly correlated in the first trimester. • DS was associated with lower free β-hCG and PAPP-A levels. • NVP was associated with higher free β-hCG and PAPP-A levels. • NVP and DS may be functionally similar but appear to have different proximal causes. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to confirm a difference in the first-trimester screen maternal biochemistry and false-positive rates (FPR) between pregnancies conceived spontaneously and those conceived via assisted reproductive technologies (ART). Methods: Retrospective analysis of the complete population of women (17,889 pregnancies) who had undergone first-trimester screening between January 2004 and September 2009 at three private ultrasound clinics in Queensland, Australia was used in the study. The age, gestation, method of conception, ultrasound markers, biochemistry markers (PAPP-A, fβ-hCG), and type of biochemical analyzer platform (Brahms Kryptor, Immulite 2000) data was collated. Univariate analysis of variance (ANOVA), Spearman's rank nonparametric correlation analysis, and Binary Logistic Regression analysis were used to analyze data. Spontaneous pregnancies were used as controls. Results were considered significant when the p value was less than 0.05. Results: After exclusions, 16,363 singleton pregnancies, including 1543 conceived via ART, were analyzed. Results from the two biochemistry platforms, Brahms Kryptor and Immulite 2000 were significantly different ( p < 0.001); thus, the data was divided for analysis purposes. PAPP-A was universally significantly lower in IVF pregnancies compared to spontaneously conceived pregnancies ( p < 0.001). Using the Brahms Kryptor platform, ICSI was associated with significantly decreased PAPP-A ( p < 0.046), and a significantly increased FPR ( p = 0.012). Conclusions: Consistent with previous studies IVF pregnancies had significantly lower PAPP-A levels supporting the need to appropriately adjust the combined first-trimester screening (cFTS) risk algorithm for IVF conceptions. The Brahms Kryptor and Immulite 2000 platforms are significantly different; however, the universally lower PAPP-A findings support the hypothesis that the lower PAPP-A is due to a biological cause. [ABSTRACT FROM AUTHOR]

Objectives: To compare the screening performances of combined screening test risk algorithm for trisomy 18 (T18) using various cutoffs with a multiparameter ultrasound-based method. To compare the general and maternal age (MA)-based screening performances for T18 by means of combined screening and an ultrasound-based method.Methods: This was a prospective, multicenter study based on a mixed-risk non-selected population of women referred to referral centers for a first-trimester screening. Each subject was offered a choice between either a traditional combined screening (CSG arm) or an ultrasound-based screening (USG arm). General and MA-based screening performances were measured.Results: The study population comprised 10 820 pregnancies as follows: 5132 in the CSG arm, including 28 cases of T18, and 5688 in the USG arm, including 29 cases of T18. In the CSG arm, the detection rate (DR) for T18 at a false-positive rate (FPR) of 3% was 86%, whereas the DR was 100% for the USG arm. MA influenced the T18 screening performance in the CSG arm and reduced the DR in MA ranges  <26 years and 31-35 years. This influence was not observed in the USG arm.Conclusions: Only, a multiparameter ultrasound-based screening method may be considered an effective alternative to combined screening for T18 screening. The technique exhibits high and stable DRs irrespective of MA. [ABSTRACT FROM AUTHOR]

Objective: Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus (GDM). This study aims to explore the performance of a panel of first-trimester biochemical markers for the prediction of GDM. Methods: A case–control study was performed that included 12 women who developed GDM and 60 controls matched for maternal and gestational age at blood collection. Levels of pregnancy-associated plasma protein A (PAPP-A), soluble endoglin, pregnancy protein 13, and adiponectin (Adipo) were measured on residual sera used in first-trimester screening for Down syndrome. Data were analyzed by nonparametric methods. A receiver operating characteristic curve was used to calculate the detection rate (DR) obtained with a panel of significant predictors for GDM. Results: Multiples of the median values for Adipo and PAPP-A were significantly reduced in GDM cases versus matched controls. Combination of Adipo and PAPP-A yielded a DR of 63.6% at a false-positive rate of 10%. Addition of body mass index (BMI) to this panel increased DR to 72.7%. Conclusion: This study suggests that first-trimester screening with Adipo, PAPP-A, and BMI may effectively identify women at high risk for the development of GDM. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between pregnancy-associated placental protein A (PAPP-A) levels in the first trimester of pregnancy and adverse pregnancy outcomes.Method: A retrospective study included data from a group of patients in the first trimester of pregnancy with PAPP-A levels below 0.3 multiples of median who attended the Helsinki University Hospital, Finland, between January 1, 2009 and December 31, 2012; an age-matched control group of patients with PAPP-A levels 0.9-1.1 multiples of median was also enrolled. The incidences of adverse pregnancy outcomes in the two groups were compared.Results: There were 961 patients included in each of the groups. Significantly increased risks of aneuploidies (odds ratio [OR] 116.0; 95% confidence interval [CI] 16.2-836.6) and spontaneous abortion (OR 7.7; 95% CI 2.7-22.0) were observed among patients with low PAPP-A (both P<0.001). Preterm delivery (OR 2.5, 95% CI 1.8-3.5), pre-eclampsia (OR 10.9, 95% CI 4.3-27.6), and small for gestational age neonates (OR 4.9, 95% CI 3.2-7.5) were also observed more frequently among patients with low PAPP-A (all P<0.001). There were 9 (0.9%) stillbirths recorded among patients with low PAPP-A and none recorded in the control group.Conclusion: Low PAPP-A was associated with adverse pregnancy outcomes and aneuploidy. These risks should be considered when planning follow-up for patients with low PAPP-A pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate first trimester pregnancy-associated plasma protein-A (PAPP-A) and birth weight percentile.Study Design: Included were women who underwent first trimester prenatal screening through the California Prenatal Screening Program with expected dates of delivery between August 2009 and December 2010, linked birth certificate and hospital discharge records, known birth weight, and no chromosomal abnormality (n=134.105). PAPP-A results were reported as multiples of the median. The frequency of small or large for gestational age (SGA, ≤10%; LGA, ≥90%) versus appropriately grown for gestational age birth was examined by PAPP-A percentile. Patterns were studied by gestational age at delivery. Relative risks (RRs) and their 95% confidence intervals were adjusted for race/ethnicity.Results: Women with PAPP-A ≤10th percentile and an infant born after 32 weeks were increasingly more likely to have an SGA infant (adjRRs 1.5-4.6) as the PAPP-A percentile declined, and were increasingly less like to have an LGA infant born at term (adjRRs 0.5-0.7) compared to women with PAPP-A measurement >10th to <90th percentile. PAPP-A ≥90th percentile was protective for SGA among infants born after 32 weeks gestation (adjRRs 0.3-0.7) and was associated with LGA among infants born at term (adjRRs 1.2-8.2).Conclusion: Women with PAPP-A ≤10th percentile are more likely to have an SGA infant at all gestational ages. PAPP-A ≥90th percentile is protective against SGA and is associated with an increased risk of LGA for infants born after 32 weeks gestation. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques from blastocyst transfer, with or without cryopreservation.Study Design: retrospective case-control analysis involving 298 singleton pregnancies with euploid fetuses recruited between 2012 and 2014. Forty-seven women conceived with fresh blastocysts from in vitro fertilization cycles (fresh-blasto), 51 with frozen-thawed blastocysts (frozen-blasto) and 200 were natural conceptions (controls). All cases underwent ultrasound assessment at 11(+0)-13(+6) weeks with measurements of crown rump length, nuchal translucency, free β-hCG and PAPP-A concentrations. The outcome of pregnancy was recorded (gestational age at birth, birth weight, obstetric complications).Results: Baseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The median delta nuchal translucency was significantly higher both in frozen-blasto group (median: 0.27mm; Interquartile Range [IQR]: 0.02-0.44; p<0.001) and in fresh-blasto group (median: 0.17mm; IQR: 0.04-0.39; p=0.014) as compared to control group (median: 0.06mm; IQR: -0.08 to 0.20), whereas it was not different in the frozen-blasto compared to the fresh-blasto group. The median free β-hCG multiples of the median (MoMs) was significantly higher both in frozen-blasto group (median 1.15; IQR 0.83-2.11; p=0.001) and in fresh-blasto group (median 0.95; IQR 0.52-1.48; p=0.001) as compared to control group (median 0.99; IQR 0.57-1.26), and it was also higher in frozen-blasto group compared to fresh-blasto group (p<0.001). The three groups showed no significant differences in the median PAPP-A MoMs. The median delta crown rump length was also not significantly different among the three groups.Conclusions: in assisted reproduction technique pregnancies from blastocyst transfer, with or without cryopreservation, both the nuchal translucency measurement and free β-hCG concentration are higher as compared to spontaneous conceptions, whereas PAPP-A does not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of maternal factors, biomarkers, and uterine-artery Doppler in the prediction of hypertension during pregnancy.Methods: A prospective cohort study was performed between December 2012 and November 2014. All singleton pregnancies between 11 weeks and 13 weeks, 6 days of pregnancy were included. Patients had their body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), mean arterial pressure, uterine-artery Doppler pulsatility index, and pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin levels recorded. Any patients diagnosed with hypertension during follow-up were assigned to the case cohort; all other patients were assigned to the control group.Results: Hypertension during pregnancy was observed in 198 (9.7%) of 2042 patients that attended follow-up. The mean BMI, mean arterial pressure, uterine-artery Doppler pulsatility index, and the PAPP-A level at study enrollment were all significantly correlated with the later development of hypertension (P<0.001 for all variables). The combined sensitivity, specificity, positive predictive value, and negative predictive value of using the investigated parameters to predict hypertension was 76%, 80%, 31%, and 93%, respectively.Conclusion: Patient BMI, mean arterial pressure, PAPP-A, and pulsatility index were found to be effective predictors of hypertension during pregnancy. Combining these predictors may be beneficial in selecting individuals for close monitoring and early intervention during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine whether there is a difference between the known gestational age in pregnancies conceived after IVF and the estimated gestational age based on the crown-rump length (CRL) measurement during the first trimester.Design: We retrospectively (between 2007 and 2012) studied a cohort of 6,739 patients who underwent ultrasonography between 11 and 13+6 weeks of amenorrhea.Setting: Hospital.Patient(s): Group A consisted of 6,621 patients with regular menses whose term was calculated based on the date of their last menstrual period (LMP). Group B consisted of 529 patients whose pregnancies had been achieved by IVF and in whom term was calculated based on the date of fresh or frozen ET.Intervention(s): None.Main Outcome Measure(s): The gestational age difference was obtained by comparing the age obtained by measuring the CRL (Robinson's curve) with the gestational age calculated in accordance with LMP in group A or with ET day in group B.Result(s): The gestational age difference was significantly more in group B (2.3 days vs. 0.84 days in group A). We found a significant difference regarding biochemical markers for trisomy 21 to the detriment of group B with a significantly reduced pregnancy-associated protein P-A multiple of median (0.78 vs. 0.92).Conclusion(s): There appears to be a small difference in CRL development between spontaneous pregnancies and pregnancies conceived by assisted reproductive technology (ART). Specific ultrasonographic curves for pregnancies conceived by ART would be more relevant and precise. The underlying pathophysiological mechanisms are not very clear and offer possibilities for future research. [ABSTRACT FROM AUTHOR]

Objective: To examine the role of first-trimester uterine artery Doppler, serum β-hCG and pregnancy-associated placental protein-A (PAPP-A) in prediction of preeclampsia and IUGR.Methods: A total of 100 pregnant women in the 11-14 weeks' gestation were examined using uterine artery Doppler, serum β-hCG and PAPP-A. All women were followed-up for development of preeclampsia or IUGR.Results: A total of 94 women completed the study of which 7 (7.4%) developed complications. Uterine artery PI and RI were significantly higher whereas serum β-hCG and PAPP-A levels were significantly reduced in patients who developed complications when compared with those who did not. Uterine artery PI had the highest sensitivity (100%) but a low specificity (56% and 45%) in prediction of preeclampsia and IUGR, respectively. Adding PAPP-A to uterine artery PI elevated the specificity into 94.44% and 95.51%, respectively. Combined PI and β-hCG elevated the specificity into 88.89% and 89.89%, respectively.Conclusion: Our study suggests that first-trimester uterine artery impedance, as measured by Doppler ultrasound as well as low serum biomarkers (β-hCG and PAPP-A) can be used for prediction of preeclampsia and IUGR. The most sensitive is uterine artery PI. Adding β-hCG to PI improves specificity in prediction of both preeclampsia and IUGR. Uterine artery PI plus PAPP-A is the best combination for prediction of both preeclampsia and IUGR. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia is a serious disease which may result in maternal and neonatal mortality and morbidity. Improving the outcome for preeclampsia necessitates early prediction of the disease to identify women at high risk. Measuring blood cell subtype ratios, such as the neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios, might provide prognostic and diagnostic clues to diseases. Aim: To investigate hematological changes in early pregnancy, using simple complete blood count (CBC) and blood concentrations of beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) to determine whether these measures are of any value in the prediction and early diagnosis of preeclampsia. Materials and Methods: Six hundred fourteen consecutive pregnant women with preeclampsia (288 with mild disease and 326 with severe disease) and 320 uncomplicated pregnant women were included in the study. Blood samples for routine CBC and first trimester screen, which combines PAPP-A and free β-hCG blood concentrations, were analyzed. Results: The NLR values were significantly higher in the severe preeclampsia group compared with the control group (p<0.001). We also confirmed that levels of PAPP-A were lower in patients who developed preeclampsia. Conclusion: Because measuring CBC parameters, particularly NLR, is fast and easily applicable, they may be used to predict preeclampsia. [ABSTRACT FROM AUTHOR]

Objective To examine whether differences exist in routine first trimester maternal serum screening analyte measurements between normal pregnancies, placenta praevia and abnormally invasive placentation ( AIP). Design Multidisciplinary audit. Setting Associated university teaching hospital with 9000 annual deliveries. Population Five hundred and sixteen pregnancies in total, including 344 normal controls, 17 with AIP and 155 placenta praevia cases. Methods Comparison of maternal serum free β hCG and PAPP-A MoMs distribution in pregnancies with abnormally invasive placentation, placenta praevia and normal controls, after correcting for known confounding factors between October 2005 and September 2013. Data from a previously published first trimester AIP and biochemistry study were combined with our study data and compared in the above way to complete the analysis. Main outcome measures Differences in first trimester maternal serum PAPP-A and free β hCG in AIP, placenta praevia, and normal pregnancies. Results Median free β hCG MoM in the control group was 1.04, and 1.08 ( P = 0.859) in the placenta praevia group compared with 0.81 in the AIP group ( P = 0.06). Median PAPP-A MoM was 1.01 in the control group and 1.05 ( P = 0.83) in praevia, compared with 1.22 in AIP cases (0.16). The combined AIP dataset gave an overall PAPP-A median MoM of 1.40, and free β hCG of 0.85. Both markers showed a significantly different distribution from controls ( PAPP-A P = 0.002 and free β hCG P = 0.031). Conclusions There may be differences between first trimester maternal serum biochemical markers between normal pregnancies and those complicated by abnormally invasive placentation. If upheld, this may provide useful information for the early identification of abnormally invasive placentation. More studies are required. [ABSTRACT FROM AUTHOR]

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Objective: To determine the association between first trimester serum markers and pregnancy complications such as SGA and preterm delivery in twin pregnancies. Methods: The study included 86 multiple pregnancies. Total study population divided into three study groups as follows: very preterm pregnancies (<32 weeks), preterm pregnancies (≥32 and <37 weeks) and term pregnancies (≥37 weeks). PAPP-A, free β-hCG and birth weight percentile differences between study groups were tested for statistical significance. Results: According to birth weight percentiles, there was statistically significant difference between very preterm-preterm and very preterm-term groups (p<0.05). PAPP-A and free β-hCG medians for each group were not significantly different (p>0.05). PAPP-A levels below 5th percentile were associated with low birth weight percentiles in twin pregnancies (OR=0.968, 95% CI for OR 0.945-0.992, p=0.008). However, significant association with free β-hCG was not found regarding SGA. Conclusion: First trimester maternal serum PAPP-A can be used to predict pregnancy complications like SGA in twin pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To assess the possible changes in first trimester screening test parameters in pregnancies complicated with placenta previa and to determine whether there is an association between hyperemesis gravidarum and placenta previa. Material and Methods: A total of 131 singleton spontaneously conceived pregnancies that were complicated by placenta previa and delivered between May 2006 and May 2013 were evaluated from birth charts. Ninety patients without placenta previa were selected amongst patients who delivered within the same period of time as the control group. Cases of low lying placenta (n=52) within the study group were assessed as a separate group. The rest of the cases was considered to be in a different group. Results: Beta human chorionic gonadotropin (BhCG) multiples of medians (MoMs) and nuchal translucency (NT) MoMs were significantly higher in the placenta previa group in comparison with the low lying placenta and control groups. Apgar scores at both the 1st and 5th minutes were significantly lower in the placenta previa group. Hyperemesis gravidarum was found to be significantly more frequent in the placenta previa group. Conclusion: The prevalence of hyperemesis gravidarum in the first trimester is higher in pregnancies complicated by placenta previa. Paying more attention to the development of placenta previa in the routine pregnancy follow-up of patients with hyperemesis gravidarum could be considered. [ABSTRACT FROM AUTHOR]

Screening for Down Syndrome was initially only related to maternal age and has successively developed by introducing biochemical markers and algorithms to estimate the risk for particularly trisomy 21 and 18. We now have a long experience of screening with four biochemical markers, alpha-fetoprotein, total hCG, unconjugated estriol and free β-hCG during the second trimester. Screening is now moving towards screening in the first trimester using a combination of ultrasound (Nuchal Translucency) and the maternal serum biochemical markers free β-hCG and Pregnancy Associated Plasma Protein-A (PAPP-A). This has become known as the combined test. Several maternal and pregnancy factors which can influence the concentrations of biochemical markers are discussed. The possibilities of screening for other aneuploidies in the first trimester and an outline of recent methods to improve overall screening performance are highlighted and the review will suggest some possible options for the future in which Cell Free DNA techniques may become part of an improved overall screening strategy. In conclusion it is emphasized that the time has come to invert the Pyramid of Antenatal Care to focus on the 11-13 week assessment. [ABSTRACT FROM AUTHOR]

The first trimester combined screening, which analyzes fetal nuchal translucency and levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum, is routinely used to detect abnormal pregnancies associated with Down syndrome and other trisomy aneuploidies. Based on the hypothesis that major chromosomal translocations could lead to similar biochemical and developmental outcomes during early embryo development, we compared these markers among pregnancies with normal, balanced, or unbalanced fetal karyotypes. Among the parents, 71 (73%) carry balanced reciprocal translocation and 26 (27%) have Robertsonian translocation. Of the 97 pregnancies tested, 39 (40%), 37 (37%), and 22 (23%) fetuses had normal karyotype, balanced chromosomal translocations, and unbalanced chromosomal translocations, respectively. Importantly, we found that pregnancies with an unbalanced translocation had significantly higher free β-hCG multiple of the median (MoM) and larger nuchal translucency thickness than those with normal karyotype or balanced translocations. Analysis showed that the area under a receiver operating characteristic curve (AUC) is 0.716, 0.820, and 0.936 for free β-hCG MoM, PAPP-A MoM, and fetal nuchal translucency, respectively. When these 3 independent factors were combined, the AUC reached 0.976. In addition, logistic regression showed that the most optimal model for predicting an unbalanced chromosomal translocation is a combination of PAPP-A and nuchal translucency with an AUC of 0.980. Therefore, the first trimester combined screening is not only effective in the screening of Down syndrome and other trisomy abnormalities but also has high sensitivity for the detection of unbalanced chromosomal translocations in fetuses. [ABSTRACT FROM AUTHOR]

Objective: To determine whether inherited thrombophilia affects components of first trimester combined aneuploidy screening test. Method: A case-control study was performed between January 1st and December 31st 2011, at a tertiary referral hospital. Singleton pregnancies with inherited thrombophilia that underwent first trimester (11-13+6 week) combined aneuploidy screening test were included in the study. Pregnancy associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (fbHCG) and fetal nuchal translucency (NT) were compared between the study group and controls. Results: Within the study period, 15 881 women with singleton pregnancies had a combined first trimester aneuploidy screening test at our institution. Among these, 207 women met the inclusion criteria. A control group that comprised 625 women with similar gestational age was generated, using a 1:3 ratio. PAPP-A levels were significantly higher, whereas fbHCG levels and fetal NT measurements were lower in women with inherited thrombophilia ( p < 0.001). Conclusion: Our study suggested that PAPP-A, free b-HCG and NT MoM levels display alterations in women with inherited thrombophilia. Future trials are needed to assess the need for readjustment of risk in these patients. [ABSTRACT FROM AUTHOR]

Aims: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11-14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. Methods: Prospective observational study on 240 fetuses at 11-14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. Results: FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=-0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status ( t-test, P=0.149) and mode of conception ( t-test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=-0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P<0.0001). Conclusions: FV is strongly related to PAPP-A even after adjustment for crown rump length with a mechanism unrelated to placental perfusion. FV is independent of the vast majority of first trimester parameters; hence, it is a promising marker of early fetal growth. [ABSTRACT FROM AUTHOR]

Objective: To validate previously computed correction factors for free β-human chorionic gonadotrophin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies with hormone treatment and to determine the effect on false-positive rate (FPR). Methods: Retrospective study on 249 IVF and 250 ICSI cases and 20,190 controls. Correction factors 1.42 (PAPP-A), 1.17 (fβ-hCG) in IVF; 1.56 (PAPP-A) in ICSI were applied on the absolute serum concentrations. Analysis was done on log10-transformed multiples of medians (MoMs). Results: In the controls, mean PAPP-A and fβ-hCG MoM were 1.004 and 1.062. Before correction, mean PAPP-A MoM was significantly lower in IVF (0.757; p < 0.001) and in ICSI (0.671; p < 0.001) and after correction comparable (1.071; p = 0.053 in IVF; 1.048; p = 0.178 in ICSI). Before correction, mean fβ-hCG MoM was comparable (1.054; p = 0.59 in IVF and 1.051; p = 0.56 in ICSI) and after correction significantly higher in IVF (1.241; p < 0.001). After correction the likelihood for receiving a false-positive result was 1.03 in IVF pregnancies (95% CI 0.98-1.09; p = 0.248) and 1.02 in ICSI pregnancies (95% CI 0.97-1.07; p = 0.448). Conclusions: After correction the FPR in IVF and ICSI pregnancies with hormone treatment reduces to the observed FPR in the controls. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents information on a study on the link between gestational diabetes mellitus and first trimester aneuploidy screening markers. A study was conducted to establish whether PAPP-A and free hCG concentrations are altered in pregnancies, which are diagnosed by an oral glucose tolerance test with gestational diabetes mellitus.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin β (free-β-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and β-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and β-hCG MoM values remain independent risk factors for fetal-T21. [ABSTRACT FROM AUTHOR]

Purpose: The role of thyroid function in biochemical markers of first trimester screening has not been assessed. The aim of the present study was to investigate if there were any relation between maternal thyroid hormones and free-beta subunit of human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels as the biochemical markers of the combined first trimester aneuploidy screening. Methods: 375 pregnant women between 11 and 14 weeks of gestation who were offered routine first trimester prenatal aneuploidy screening and whose thyroid hormone levels (Thyroid stimulating hormone (TSH), free and total thyroxine, free and total triiodothyronine, anti thyroid peroxidase antibody) were measured were assessed. Correlation of free-β-hCG and PAPP-A with maternal thyroid hormones was analyzed. Results: There was no statistically significant correlation between maternal TSH, free and total thyroxine, free and total triiodothyronine, anti-thyroid peroxidase antibodies and free-β-hCG and PAPP-A as biochemical markers of first trimester aneuploidy screening. Conclusion: Maternal thyroid function does not seem to affect secretion of fβ-hCG and PAPP-A. [ABSTRACT FROM AUTHOR]

In this study, we investigated whether the concentrations of pregnancy-associated plasma protein-A (PAPP-A) or free β-hCG (fβhCG) in the first trimester can identify women at increased risk of subsequent preterm delivery in the absence of hypertensive disorders. Preterm and early preterm deliveries are defined as those deliveries before completing 37 and 34 weeks, respectively. A total of 868 women were enrolled into this study. According to the level of the markers, the patients were evaluated in three groups: 1 - maternal serum level ≤5th percentile, 2 - between 5th and 95th percentiles, 3 - ≥95th percentile. In the group of patients with a PAPP-A level ≤5th percentile [≤0.35 multiples of the median (MoM)], mean gestational age (GA) at delivery, mean birth weight and the number of the cases with early preterm delivery were significantly lower than the others. Mean level of PAPP-A was significantly lower in cases with early preterm than term deliveries (0.58 ± 0.32 versus1.09 ± 0.69; p = 0.01). Maternal serum level of fβhCG did not show significant difference between these groups (0.84 ± 0.45 versus 1.17 ± 0.77; p = 0.15). Low levels of maternal serum PAPP-A (≤0.35 MoM) (Odds ratio = 7; 95% confidence interval 1.8-27.7; p = 0.0048) significantly predicted early preterm delivery in normotensive pregnancies. Women with low levels of PAPP-A at first trimester have a higher risk of early preterm delivery even in the absence of hypertensive disorders. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to state the role of first trimester pregnancy-associated plasma protein A (PAPP-A)-multiple of the median (MoM) value as a predictor for breech presentation at term of pregnancy. Materials and methods: In this retrospective study, we present data for 1100 singleton full-term deliveries that took place in a third-level hospital setting in northeast Italy between January 2004 and July 2007. For each case, PAPP-A, free beta-human chorionic gonadotropin and nuchal translucency were measured during prenatal trisomies screening (between 11 weeks and 13 weeks and 6 d). A wide range of predictive factors for breech presentation at term of pregnancy and other confounding elements were considered. Results: Of the 1100 singleton deliveries at term considered in our study, 40 babies were in breech presentation. Using bivariate analysis and multivariate logistic regression, a lower PAPP-A MoM than 0.63 (first quartile of our distribution) in the first trimester (OR 2.41, CI.95 1.25-4.67), and placental index at term higher than the median value (OR 2.04, CI.95 1.00-4.17) were proven to be associated with breech presentation at term. Conclusions: A low PAPP-A during the first trimester was a predictive factor for breech presentation at term of pregnancy. Acknowledging and acting on this predictor could enable improved management of breech foetuses in the future. [ABSTRACT FROM AUTHOR]

Objective To examine placental growth factor (PIGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening. Methods PIGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free β-human chorionic gonadotro pin (β-hCG) and pregnancy- associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PIGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free β-hCG and PIGF for 20000 euploid and 20 000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free β-hCG, PAPP-A and PIGF, PA PP-A and PIGF or free β-hCG and PIGF, and detection and false-positive rates were calculated. Results Median PIGF-MoM was 1.0 (95% confidence interval (Cl), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% Cl, 0.70-0.76), in trisomy-21 fetuses (P <0.0001). There was no significant dependency between PIGF-MoM and either gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample stor- age time (r = 0.028, P = 0.785). Modeled detection and false-positive rates for first-trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PIGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PIGF increased the detection rate to 87% and reduced the false-positive rate to 2.6%. Screening by maternal age and fetal NT in combination with PIGF and PAPP-A or in combination with PIGF and free β-hCG provided detection rates of 82% and 79%, with false-positive rates of 2.7% and 3.0%, respectively. Conclusion In pregnancies with trisomy 21 P1GF is reduced. The impact on the overall screening performance for trisomy 21 is low and does not justify the measurement of PIGF solely for trisomy 21 screening. However, as PIGF is measured with the aim of assessing the risk for pre- eclampsia, further improvement in screening for trisomy 21 can be considered as an added benefit. [ABSTRACT FROM AUTHOR]

Objective To prospectively evaluate the performance of first-trimester combined screening for trisomy 21 using the biochemical markers pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (free β-hCG) obtained before and at the time of the nuchal translucency (NT) scan. Methods Three fetal medicine departments in Denmark participated in the study. Screening for trisomy 21 was set up as a two-step approach with blood sampling performed before the NT scan (early sample) and again at the time of the NT scan (late sample). PAPP-A and free β-hCG were measured on both the early and late samples. Age-standardized detection and false-positive rates for different screening protocols were calculated. Results We collected two blood samples in 27 pregnancies affected by trisomy 21 and in 3891 control pregnancies. The early samples were taken between gestational ages 8 + 0 and 13 + 6 weeks, and the late samples between 11 + 3 and 14 + 6 weeks. The median interval between the samples was 17 (range, 1-40) days. We found a significantly better estimated screening performance when using early sampling vs late sampling ( P < 0.05). With a risk cut-off of 1 in 100, at the time of the risk assessment the estimated detection and false-positive rates when using the early sample were 91% (95% CI, 81-98%) and 1.6% (95% CI, 1.3-2.0%), respectively. For fixed false-positive rates the highest detection rates were achieved using both blood samples. When comparing early sampling vs double sampling there was no significant difference in screening performance. Conclusion In combined first-trimester screening for trisomy 21, use of early sampling with measurement of PAPP-A and free β-hCG before the time of the NT scan can optimize screening performance. Using maternal serum markers obtained both before and at the time of the NT scan has the potential to further improve performance, but larger studies are needed to confirm this potential. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]