Pregnancy-associated Plasma protein-A Values Research Articles

Competing‐risks model for prediction of small‐for‐gestational‐age neonate from maternal characteristics, serum pregnancy‐associated plasma protein‐A and placental growth factor at 11–13 weeks' gestation

To expand a new competing-risks model for prediction of a small-for-gestational-age (SGA) neonate, by the addition of pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF), and to evaluate and compare PAPP-A and PlGF in predicting SGA. This was a prospective observational study of 60 875 women with singleton pregnancy undergoing routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation. We fitted a folded-plane regression model for the PAPP-A and PlGF likelihoods. A previously developed maternal history model and the likelihood models were combined, according to Bayes' theorem, to obtain individualized distributions for gestational age (GA) at delivery and birth-weight Z-score. We assessed the discrimination and calibration of the model. McNemar's test was used to compare the detection rates for SGA with, without or independently of pre-eclampsia (PE) occurrence, of different combinations of maternal history, PAPP-A and PlGF, for a fixed false-positive rate. The distributions of PAPP-A and PlGF depend on both GA at delivery and birth-weight Z-score, in the same continuous likelihood, according to a folded-plane regression model. The new approach offers the capability for risk computation for any desired birth-weight Z-score and GA at delivery cut-off. PlGF was consistently and significantly better than PAPP-A in predicting SGA delivered before 37 weeks, especially in cases with co-existence of PE. PAPP-A had similar performance to PlGF for the prediction of SGA without PE. At a fixed false-positive rate of 10%, the combination of maternal history, PlGF and PAPP-A predicted 33.8%, 43.8% and 48.4% of all cases of a SGA neonate with birth weight < 10th percentile delivered at ≥ 37, < 37 and < 32 weeks' gestation, respectively. The respective values for birth weight < 3rd percentile were 38.6%, 48.7% and 51.0%. The new model performed well in terms of risk calibration. The combination of PAPP-A and PlGF values with maternal characteristics, according to Bayes' theorem, improves prediction of SGA. PlGF is a better predictor of SGA than PAPP-A, especially when PE is present. The new competing-risks model for SGA can be tailored to each pregnancy and to the relevant clinical requirements. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal hemodynamic assessment by USCOM® device in the first trimester of pregnancy

Background Preeclampsia is a main obstetric disease and could be caused by the inability of the woman hemodynamic system to face the cardiovascular effort required by gestation. Objective The aim of the present study is to evaluate the correlation between maternal hemodynamic parameters detected by UltraSonic Cardiac Output Monitor (USCOM®) and ultrasound or biochemical parameters in women during the first-trimester screening of chromosomal abnormalities. Methods This was a prospective observational study with 162 women enrolled during the first-trimester ultrasound, recording demographic, biochemical and ultrasound data, including the pulsatility index of uterine arteries (UTPI). Hemodynamic indices were obtained using the USCOM® system. We also analyzed the outcomes of pregnancy of those women who delivered in our clinic. Results As for the correlation between biochemical and ultrasound parameters, pregnancy-associated plasma protein A (PAPP-A) relates inversely with the mean UTPI (r s −0.298, p < .001). We also reported a statistically significant correlation between the mean UTPI and the maternal haemodynamic parameters detected by USCOM® (higher values of mean UTPI are associated with lower values of indexed cardiac output, CO, and higher indexed peripheral resistances, TVR). When comparing women with higher UTPI and TVR or lower CO to patients who had regular values of these parameters, we noticed that between these groups there were significant differences in all the remaining hemodynamic parameters, including inotropy index and stroke volume, as well as in the biochemical values of PAPP-A. Analyzing postpartum data, if we combine the onset of hypertensive disorders and fetal growth restriction, the most predictive parameter is indexed TVR. Conclusion Our study confirmed the correlation between PAPP-A and placental function, expressed through the determination of the pulsatility index of the uterine arteries. Moreover, we found a clear correlation between biochemical markers, placental function and maternal hemodynamics, since the first trimester of pregnancy. The inclusion of maternal hemodynamic evaluation could be useful in the screening protocols of preeclampsia. If we combine the onset of hypertensive disorders and of fetal growth restriction, the most predictive parameter is indexed total vascular resistances.

Fetal fraction of cell free DNA in screening for hypertensive disorders at 11–13 weeks

Objective To investigate whether first-trimester maternal plasma fetal fraction is altered in women that subsequently develop preeclampsia (PE) or gestational hypertension (GH) and to examine its potential value in improving the performance of screening for PE and GH by maternal factors and maternal serum pregnancy associated plasma protein-A (PAPP-A), mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI). Methods The study population of 10,131 pregnancies undergoing cell free fetal DNA testing at 11–13 weeks’ gestation included 91 (0.9%) cases with preterm-PE, 222 (2.2%) cases with term-PE, 360 (3.6%) with GH and 9,458 (93.4%) cases unaffected by hypertensive disorders. Maternal plasma fetal fraction levels were expressed as multiples of the median (MoM) after adjustment for maternal factors and crown-rump length. The performance of screening for preterm-PE, term PE and GH by maternal factors and MoM values of fetal fraction, PAPP-A, UtA-PI and MAP was evaluated by receiver operating characteristic (ROC) curves. Results The median fetal fraction MoM was significantly lower in the preterm-PE (0.825; IQR 0.689–1.115 MoM, p < .001), term-PE (0.946; IQR 0.728–1.211 MoM, p = .028) and GH (0.928; IQR 0.711–1.182 MoM, p < .001) groups than in the unaffected group (1.002; IQR 0.785–1.251 MoM). However, the performance of screening for PE or GH by maternal factors alone or by maternal factors and PAPP-A, UtA-PI and MAP was not significantly improved by the addition of fetal fraction. Conclusions First trimester maternal plasma fetal fraction is not useful in screening for hypertensive disorders of pregnancy.

Correlation of PAPP-A values with maternal characteristics, biochemical and ultrasonographic markers of pregrancy

Objective: Our aim is to investigate whether there is a correlation of pregnancy-associated plasma protein A (PAPP-A) values with other variables in pregnancy and maternal characteristics. Materials and Methods: We retrospectively analyzed the relation between the pregnancy-associated plasma protein A levels, demographics, biochemical and ultrasonographic markers of the first trimester screening of 11,842 pregnant women seen at a tertiary hospital between November 2002 and November 2008. Results: A significant difference between PAPP-A values of the diabetic and non-diabetic pregnant women were observed (p=0.0005, Mann-Whitney U test). In terms of weight, crown-rump length, BetahCG values, significant differences were observed between low and medium level PAPP-A subgroups and between low and high level PAPP-A subgroups. PAPP-A levels were found to differ significantly between the pregnant women of Caucasian origin and other racial origins. Conclusions: Pregnant women with different ethnic and medical backgrounds have different PAPP-A values and other markers of the aneupleudity screening. To make patient specific risk predictions, understanding these interactions and differences is important. Future studies are needed to understand the pathopyhsiology behind these differences.

Antenatal fetal death in multiple pregnancy: is early prediction possible?

Introduction. Perinatal mortality in multiple pregnancies increases by 8–10 times compared to singletons. Stillbirth is a significant part of all complications of multiple pregnancies. Although the incidence of perinatal mortality in multiple pregnancies has decreased consistently compared to extremely high rates in the past, it remains relatively high, despite significant positive changes in the management of such pregnancies. Aim: to assess the diagnostic potential of the first trimester's biochemical screening in multiple pregnancies for predicting antenatal fetal death. Materials and Methods. As part of a retrospective study, a cohort of twin pregnancies after in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or spontaneous conception underwent screening of the first trimester at 11+0–13+6 weeks of gestation as recommended by the Fetal Medicine Foundation. Determination of pregnancy-associated plasma protein-A (PAPP-A) in blood serum with subsequent calculation of the relative PAPP-A MoM (multiples of median) – a multiple of the median (an indicator of how much the individual test result deviates from the reference values) was performed. Results. Prenatal screening and outcomes of 302 multiple pregnancies showed that with PAPP-A MoM &lt; 0.5, antenatal fetal death occurred with a frequency of 42.86 % (6/14), with PAPP-A MoM within the reference values – In 12.67 % (28/221), with PAPP-A MoM &gt; 2.0 – in 6.7 % (2/30). Differences between patients with PAPP-A MoM &lt; 0.5 and PAPP-A MoM within the reference values, as well as PAPP-A MoM &lt; 0.5 and PAPP-A MoM &gt; 2.0 were statistically significant (p = 0.002 and p = 0.004, respectively). No differences were detected between spontaneous and assisted reproductive technology (ART) pregnancies. Conclusion. In women with multiple pregnancies resulting from ART or spontaneous, PAPP-A MoM values below the reference interval (&lt; 0.5) in the first trimester are associated with an increased risk of antenatal fetal death.

Can first trimester pregnancy-associated plasma protein-A predict the surfactant needs of preterm neonates?

Low values of pregnancy associated plasma protein A (PAPP-A), have been shown to be associated with some poor gestational outcomes, especially those related to placental deficiency such as pre-eclampsia and fetal growth restriction as well as preterm labor. The aim of this study was to compare first trimester PAPP-A MoM values with the surfactant needs of newborns of pregnant women who had a preterm delivery. This study included 216 pregnant women who had a preterm delivery, who were found to be in the low-risk group based on their aneuploidy screening. The women were separated into two groups based on the surfactant receipts of their newborns. A record was made of the obstetric history, birth characteristics of the preterm infants, and whether or not there was a need for surfactant. A comparison of the PAPP-A values of the two groups revealed that the group that received surfactant had statistically significantly lower PAPP-A values (t(-3.97) = 0.203, p < 0.001). When the cut-off value of PAPP-A was taken as 1 MoM and the gestational age was analyzed together with the birth weight, PAPP-A alone was found to be a significant independent variable for the prediction of respiratory distress syndrome (RDS) (p = 0.031; OR:8.2 (1.2-55.6)). The result of this study demonstrated that PAPP-A MoM values may be significant in predicting the need for surfactant in RDS, which is a frequently seen condition in the neonatal period.

Maternal Pregnancy Associated Plasma Protein-A Levels in Late First Trimester as a Predictor of Miscarriage- A Cross-sectional Study

Indroduction: Miscarriage is the most common complication of pregnancy. Defective implantation is one of the common causes of miscarriage. Pregnancy Associated Plasma Protein-A (PAPP-A) is secreted from syncytiotrophoblast and it enables trophoblast invasion. Few studies have shown association of PAPP-A with miscarriage. However, there is limited data available to establish the role of PAPP-A as a predictive marker of miscarriage, especially in Indian population. Aim: To determine the potential of maternal PAPP-A level estimation in asymptomatic women in late first trimester (10-13 weeks) with viable foetus in predicting subsequent miscarriage. Materials and Methods: This was an observational, cross-sectional study conducted from November 2016 to April 2018 at University College of Medical Science and Guru Teg Bahadur Hospital, Delhi, India. Asymptomatic pregnant women (N=500) at 10-13 weeks of gestation were recruited from an antenatal clinic after confirmation of foetal viability. A 2 mL of blood sample was collected and serum PAPP-A level was measured. Independent t-test and Chi-square test was used to compare continuous data and Mann-Whitney U test was used to compare PAPP-A Multiple of Median (MOM). Logistic regression was used to estimate risk of miscarriage. Results: Out of 500 participants, 9 were lost to follow-up. From remaining N=491, 32 (6.5%) women had a miscarriage. PAPP-A levels were significantly decreased in miscarriage group compared to ongoing pregnancy group with median MOM 0.116 (0.080-0.17) and 1.25 (0.665-3.249) respectively (p-value &lt;0.001). PAPP-A MOM value of ≤10th percentile sensitivity and specificity of detection of miscarriage was 81.25% and 94.98% and at ≤5th percentile sensitivity and specificity was 40.62% and 97.82%, respectively. Lower the percentile cut-off of serum PAPP-A value, higher was the specificity and positive predictive value for prediction of miscarriage. By applying logistic regression we found that if PAPP-A MOM decreases by 1 unit the chances of miscarriage increased by 1.2 times. By this model 63.2% of cases could be explained (Nagelkerke R Square=0.632). For prediction of pregnancies likely to miscarry, the area under Receiver Operator Characteristic (ROC) curve (95% CI) was 0.969 (0.955-0.983). Conclusion: Low serum PAPP-A levels from asymptomatic women in late 1st trimester is a good predictive marker of miscarriage.

Correlation of Maternal Age, Weight, Pregnancy - associated Plasma Protein A, Free Beta-human Chorionic Gonadotropin, Fetal Crown-rump Length, and Fetal Gender with Fetal DNA Fraction in Non-invasive Prenatal Testing: An Experiment on Iranian Pregnant Women

Background: Non-invasive prenatal testing (NIPT) as a novel screening method has been widely proposed to screen for common fetal chromosomal aneuploidies. The aim of the present study was to examine the possible effects of maternal age, maternal weight, fetal crown-rump length (CRL), serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin (free β-hCG), and fetal gender on cell-free fetal DNA (cffDNA) percentage fluctuations. Methods: In the present cross-sectional study, 308 singleton pregnant women aged 20-47 years at 11+0 to 13+6 weeks of pregnancy referring to the DeNA Laboratory in Tehran, Iran, for NIPT test during a one-month period between July 2018 and August 2018 were selected randomly. The cffDNA was extracted from maternal plasma. Whole exome sequencing by a ion semiconductor sequencer using cffDNA was applied for all participants. The PAPP-A and free β-hCGas biochemical biomarkers were assessed using a closed chemilumine scence immunoassay analyzer. The Shapiro-Wilk test, Pearson analysis, beta regression analysis, and Mann-Whitney U test were performed to analyze the data. Results: In the screening population, the cffDNA percentage showed no significant correlation with CRL and maternal age (P=0.096 and P=0.881, respectively). However, the cffDNA percentage correlated well with maternal weight, PAPP-A, and free β-hCG (P=0, P=0.009, and P=0.001, respectively). Beta regression between cffDNA percentage and maternal weight, free β-hCG, and PAPP-A was significant (P<0.001). The mean cffDNA percentage between male and female fetal groups showed a significant difference (P<0.001). Conclusion: This study demonstrated that the cffDNA percentage in the first trimester of pregnancy had a negative correlation with maternal weight and a positive correlation with PAPP-A and free β-hCG values. Furthermore, the cffDNA percentage in male fetuses was higher than that in female fetuses.

The significance of maternal blood pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG) levels for the risk assessment of fetal trisomy 18 during the first prenatal testing between 11 and 13+6 weeks of pregnancy.

The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing. Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of β-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18. PAPP-A and β-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and β-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and β-hCG MoM 0.2-0.5 range. Maternal free β-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal β-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and β-hCG MoMs, fetal NT measurement was an requirment.

First-trimester Combined Screening for Trisomies 21, 18, and 13 by Three Closed Chemiluminescence Immunoassay Analyzers (an Experiment on Iranian Pregnant Women)

Background: Pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (free β-hCG) as valuable biochemical biomarkers are used to screen down syndrome, Edwards syndrome, and Patau syndrome in the first trimester of pregnancy. Closed immunoassay analyzers are regarded as sophisticated platforms to measure biochemical biomarkers. This study compared the performance of three chemiluminescence analyzers when used for combined screening.Methods: The present cross-sectional study was conducted on 371 pregnant women within the age range of 20-47 years during 11+0 to 13+6 weeks of pregnancy referring to Dena laboratory in Tehran, Iran, during July 2018 and August 2018 using random selection. The biochemical biomarkers of PAPP-A and free β-hCG were assayed on Cobas, Immulite, and Maglumi analyzers. Benetech software as a commercial screening software was used to calculate the risks of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). Deming regression, nonparametric spearman analysis, analysis of variance, and Chi-square test were performed to analyze the data.Results: For the screening population, although the three systems well correlated to PAPP-A and free β-hCG, the values of Maglumi were slightly higher than those reported for Cobas and Immulite. The multiples of the median (MoM) of PAPP-A and free β-hCG had a significant correlation on three platforms. There were no significant differences between the calculated risks of T21, T18, and T13 on the three systems. The sensitivity for all systems was reported as 50%. In addition, specificity and negative predictive value (NPV) were higher than 99% and 95%, respectively. Positive predictive value (PPV) was reported as less than 50%.Conclusion: The obtained results of the present study demonstrated that there were significant correlations between three different systems in terms of PAPP-A and free β-hCG values and MoMs. The sensitivity of all systems for all trisomies was 50%; however, the specificity of all systems was almost the same. The best PPV and NPV for T21 were on Cobas, Immulite, and Maglumi, respectively. The PPV and NPV of all systems for T18/13 were almost the same.

Predictive value of pregnancy-associated plasma protein-A in relation to fetal loss: A systematic review and meta-analysis.

Background For a woman with bleeding and threatened abortion, ultrasound scan is done to confirm the viability of the fetus; however, 10-15% of the embryos are eventually aborted. Distinguishing between women with good and poor prognosis can be a helpful approach.ObjectiveThis study aimed to review the predictive value of Pregnancy-associated Plasma Protein A (PAPP-A) in relation to the diagnosis of fetal loss.Materials and MethodsThe articles published in multiple databases including Web of Science, PubMed, MEDLINE, Scopus, and Persian databases such as ISC, Magiran, and IranMedx were searched for articles published until May 2019. MeSH terms was used for searching the databases including fetal loss OR pregnancy loss OR abortion OR miscarriage with the following word using AND; Pregnancy-Associated Plasma Protein-A OR PAPP-A. Two reviewers extracted data and recorded them in a pre-defined form and assessed the quality of articles using the Newcastle-Ottawa tool. Meta-analysis was done using the Comprehensive Meta-Analysis/2.0 software and MetaDisc.Results A total number of 16 studies were eligible for the qualitative data synthesis, out of which 8 studies were included in the meta-analysis. All studies had high and medium quality. The forest plot analysis showed a sensitivity of 57% (95% CI: 53-63%), a specificity of 83% (95% CI: 80-85%), a positive likelihood ratio of 3.52 (95% CI: 2.44-5.07), a negative likelihood ratio of 0.54 (95% CI: 0.37-0.79), and a diagnostic odds ratio of 6.95 (95% CI: 3.58-13.50).ConclusionPAPP-A cannot be recommended on a routine basis for predicting fetal loss and still further research with a combination of other biomarkers is required.

Fetal fraction of cell-free DNA in pregnancies after fresh or frozen embryo transfer following assisted reproductive technologies.

Is the fetal fraction (FF) of circulating cell-free DNA (cfDNA) affected in pregnancies following ART treatment with either fresh or frozen embryo transfer (ET) compared with natural conception? This study shows a significant reduction in the FF in ART patients compared with naturally conceived pregnancies, which seems to be more pronounced after fresh ET compared with frozen ET. Non-invasive prenatal testing (NIPT) is based on cfDNA in maternal blood, of which about 10% is of placental origin and thus represents the fetal karyotype. Validation studies have demonstrated a high sensitivity, specificity and positive predictive value of NIPT for the detection of fetal trisomy 21, 18 and 13. Nevertheless, the FF of cfDNA is an important factor for NIPT test accuracy. Several studies have found a reduction in FF for pregnancies following ART in comparison with natural conception. However, knowledge on how the FF is affected in ART pregnancies after fresh ET compared with frozen ET is very limited. The study was designed as a case-control study. A total of 54 women with an ongoing pregnancy following ART treatment were included. After exclusion for different reasons, statistical analyses were based on 23 NIPT samples from pregnant women treated with fresh ET and 26 NIPT samples from pregnant women treated with frozen-thawed ET in a modified natural cycle. Women were included between February 2018 and November 2018. The results were compared with a control group of 238 naturally conceived pregnancies with a high-risk result from the combined first trimester screening (cFTS). The study included women from the Fertility Clinics at Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet. Blood samples for NIPT analysis were drawn between 11 + 0 and 14 + 2 weeks of gestation and were all analyzed at the NIPT Center at Copenhagen University Hospital Hvidovre. The NIPT-test was performed by massive-parallel whole-genome sequencing. The FF was determined using the SeqFF algorithm. We found a reduction in FF in ART patients compared with naturally conceived pregnancies, and the reduction was more pronounced for ART pregnancies after fresh ET (mean FF = 0.049) compared with frozen ET (mean FF = 0.063) (multivariate analysis adjusted for maternal BMI, P = 0.02). Another multivariate analysis, adjusted for BMI and multiples of median (MoM) values for pregnancy-associated plasma protein-A (PAPP-A), demonstrated a significantly reduced FF for ART pregnancies (mean FF = 0.056) compared with naturally conceived pregnancies (mean FF = 0.072) (P < 0.0001). We found that FF was significantly reduced with increasing maternal BMI (P < 0.0001) and with decreasing MoM values of PAPP-A (P = 0.003). A limitation of our study design was the relatively small sample size. Another limitation was that the control group was not matched with the ART-treated women. The majority of the women from the control group had a high risk from cFTS, thereby their biochemical markers were diverging. However, the biochemical markers for the ART-treated women with fresh or frozen ET were not divergent within the subgroups. Concurrent with other studies demonstrating a reduced FF for singleton pregnancies after ART treatment compared with naturally conceived pregnancies, we found a reduction in FF between the two groups. This is one of the first studies to examine FF in ART pregnancies after fresh ET compared with frozen ET, hence the existing knowledge is limited. We find that FF is even more reduced in pregnancies following fresh ET compared with frozen ET, which might possibly reflect the predisposition of being small for gestational age after fresh ET compared with natural cycle frozen ET. The study was supported by the A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal (the A.P. Møller Foundation for General Purposes). All authors declare no conflicts of interest. NA.

Comparación de biomarcadores de primer trimestre en gestantes normotensas según su grado de obesidad en el tercer trimestre

IntroductionThis study aims to improve the efficiency of aneuploidy screening in the first trimester of pregnancy by creating predictive models that serve to identify pregnant women at risk of becoming overweight or obese in the third trimester and to using them to implement preventive measures of obesity. MethodsAn ambispective, observational, primary care study was conducted in which a total of 380 records corresponding to as many pregnancies were collected. Samples were collected from patients of 6 health centres, in order to determine the following variables: age at gestation, pregnancy-associated plasma protein A (PAPP-A) (mU/ml), human chorionic gonadotropin (b-HCG) (ng/ml), sample collection week for first trimester screening, body mass index at 12 and 28 weeks gestation (BMI), TSH at 12 weeks gestation, and systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MBP, respectively) at 12 and 28 weeks gestation. The BMI variable was recoded at 28 weeks, classifying pregnant women as normal weight (BMI<25), overweight (BMI 25-29.99), or obese (BMI≥30). The recoded BMI at 28 weeks was the variable resulting from the ordinal logistic regression model. An ANOVA study of several factors was used to discern differences between arterial pressures. A 5% alpha error was accepted. ResultsThe PAPP-A and b-HCG medians measured in the first trimester are progressively lower in the groups of pregnant women with normal weight, overweight, and obesity observed in the third trimester. These values are predictors of the weight in the third trimester (ordinal logistic regression) (PAPP-A: P=.022; b-HCG: P=.002). No pregnant woman developed pre-eclampsia. The SBP, DBP, and MBP in the third trimester were significantly different (ANOVA in several factors; P<.05). DiscussionThe ordinal logistic regression demonstrates that the decrease in the observed values of PAPP-A and b-HCG in the first trimester is a predictor of the level of significant and gradual obesity in a sample of normotensive pregnant women. An ordinal regression model including the 12-week BMI was not made due to the internal collinearity that it would provide if the result variable was based on it. The predictive effect of b-HCG is more homogeneous than that of PAPP-A for the level of overweight and obesity.

Are the first-trimester levels of PAPP-A and fb-hCG predictors for obstetrical complications in diabetic pregnancy?

Objective To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM). Methods It was a retrospective cohort study. Study groups were presented: type 1 DM (n = 100), type 2 DM (n = 50), and controls (n = 25). At 11 + 0 to 13 + 6 week’s gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated. Results The study has shown that DM is associated with a high rate of perinatal complications: PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51–1.1), and type 2 DM-0.88 (IQR, 0.42–1.15) compared to the unaffected group 1.03 (IQR, 0.96–1.12; p = .025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p = .14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile: in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5–10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth. Conclusion The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy.

First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) are known to be associated with the development of pregnancy-related complications like small for gestational age infants, intrauterine fetal demise, gestational diabetes and preeclampsia. The study aims to find possible long-term correlations with the development of metabolic and cardiovascular complications in the mothers and their progeny in later life. This is a retrospective cohort study conducted on consecutive unselected women screened for chromosomal anomalies in the first trimester of pregnancy between 2004 and 2010. PAPP-A values as well as clinical data collected at childbirth were considered. A maternal and neonatal follow-up was performed through a telephone interview with the mother during 2015. The body-mass-index and the presence of cardiovascular diseases, dyslipidaemia and diabetes mellitus were evaluated. The analysis included 988 patients. The median time of follow-up was 7 years (IQR 6–9). Lower first trimester maternal blood PAPP-A quartiles were associated with small stature of the offspring (z-score 1st-2nd quartile 0.37 IQR −0.42 and 1.17 vs 3rd-4th quartile 0.67 IQR −0.17 and 1.36, p < 0.05). Furthermore, low first trimester PAPP-A in pregnancy without other gestations following the index one, in Kaplan-Meier analysis was associated to a significant increase of hypoglycemic agents use at 7 and 10 years (respectively 1.12% CI.95 0–2.38% and 5.45% CI.95 0–10.82%) compared to the control group of high first trimester PAPP-A values (0% CI.95 0–0%) (p < 0.05). Low PAPP-A serum levels in the first trimester of pregnancy are associated with short stature in offspring and de-novo development of maternal diabetes mellitus in later life.

A Study of the Association of Early Pregnancy Serum Levels of Pregnancy-Associated Plasma Protein-A with Adverse Pregnancy Outcome

Background: Decreased levels of pregnancy-associated plasma protein-A (PAPP-A) in maternal serum can be a marker not only for some chromosomal disorders and anomalies in the fetus but also specific for adverse pregnancy outcomes too, such as preeclampsia, spontaneous preterm birth, gestational diabetes, and fetal growth restriction (FGR) and to the extent of stillbirth. Hence, measurement of early pregnancy PAPP-A levels may help identify the areas of intervention for reducing the adverse outcome in later gestations. Materials and Methods: This was a prospective observational study. A total of 250 antenatal cases fulfilling the inclusion criteria were taken in the study. Early pregnancy serum levels of PAPP-A were measured for antenatal cases visiting outpatient department of tertiary level teaching hospital between 10 and 14 weeks period of gestation, and these cases were followed up for development of adverse pregnancy outcome. Results: Two hundred and thirty-five patients had normal outcomes, among which 24 patients had PAPP-A values ≤0.4 multiples of the median (MoM) and 211 patients had PAPP-A level >0.4 MoM. Twenty-nine patients out of 250 in our study group had PAPP-A level <0.4 MoM, 1 patient developed preeclampsia (P = 0.211) but underwent normal vaginal delivery at term, and 1 had FGR (P = 0.513). Three patients had preterm delivery and the PAPP-A values in preterm group were lower as compared to term group, and this result was statistically significant (P = 0.005). Conclusion: The study concludes that the patients with low early pregnancy PAPP-A levels may be deemed to develop preterm labor subsequently and effective measures may be taken to prevent the same. However, it would be prudent to replicate the study in a wider and more representative sample over multiple centers to see if the results hold true.

Predictive value of extreme low PAPP-A, free βhCG and extreme high mean uterine artery pulsatility index in the first trimester for fetal growth restriction

Background/Aim. Adverse pregnancy outcomes such as preeclampsia (PE), placental abruption (PA), fetal intrauterine growth restriction (IUGR) and stillbirth could be recognized by prenatal screening. The objective of this study was to predict IUGR by using first-trimester extremely low pregnancy-associated plasma protein-A (PAPP-A), extremely low free beta-human chorionic gonadotropin (free ?hCG) levels, and extremely high Pulsatility-index (PI) of uterine arteries, as single and combined predictors for IUGR development. Methods. This was a prospective first-trimester study analyzing singleton pregnancies at 11?13+6 weeks? gestation who underwent routine first-trimester screening at the Department of High Risk Pregnancy of the Clinic for Gynecology and Obstetrics ?Narodni front?, University of Belgrade, Serbia. First-trimester screening for PAPP-A, free ?hCG, and PI was performed in nulliparous, normotensive women with extremely low PAPP-A (PAPP-A ? 0.52 unit multiple of median ? MoM) and/or extremely low free ?hCG (free ?hCG ? 0.56 MoM) and/or extremely high PI (PI ? 2.52). Results. Of 85 pregnant women included in the final analysis, 14 (16.5%) developed IUGR. PAPP-A ? 0.52 MoM and PI ? 2.52, as single categorical variables, found to be with high predictable values for IUGR development (odds ratio ? OR = 3.064, 95% confidence interval ? CI= 0.634-14.810, p = 0.046, and OR = 2.129, 95% CI = 0.449?10.713, p = 0.021, respectively). Furthermore, the receiver operating characteristic (ROC curve identified PAPP-A and PI as continuous variables to be significant predictors of IUGR (area under curve ? AUC = 0.671, 95% CI = 0.521?0.820, p = 0.045, and AUC = 0.744, 95% CI = 0.587?0.902, p = 0.004, respectively). Conclusion. The present study suggests that the first trimester extremely low PAPP-A and increased Doppler-PI levels are single predictors of IUGR. Described model could be used in a routine daily clinical practice in resource limited settings where other parameters are not available for the prediction of IUGR development.

The utility of pregnancy associated plasma protein-A MoM values in prediction of term respiratory distress syndrome

This study aimed to investigate if the pregnancy associated plasma Protein-A (PAPP-A) multiples of median (MoM) levels could be used as a marker for the early prediction of RDS. The present study was designed with data gathered from 1773 patients who were referred to our institution for first trimester fetal chromosomal anomaly screening. First trimester PAPP-A MoM values and postnatal RDS occurrences in these pregnancies were retrospectively analysed. Of the 1773 neonates that were included in the study, 28 were delivered at or beyond 37 weeks, and 42 were delivered less than 37 weeks of gestation. In the group of neonates at or beyond 37 weeks, the cut-off value for RDS prediction was determined as 1.02. For this cut-off value, sensitivity was 72.41% and specificity was 91.84%. The area under curve (AUC) was determined to be statistically significant (p < .01). In conclusion, it was determined that in neonates that were delivered at or beyond 37 weeks of gestation, RDS occurrence could be predicted at a significant rate by utilising PAPP-A MoM values.IMPACT STATEMENTWhat is already known on this subject? Respiratory distress syndrome (RDS) is one of the major global healthcare problems, and continues to effect newborns despite the improvements in diagnosis and treatments of the disease. Studies have shown that pregnancy associated plasma protein-A (PAPP-A) has a critical role in cellular proliferation and differentiation, and it is closely associated with many physiological and pathological processes via regulation of local insulin like growth factor (IGF) concentrations. In majority of the past studies in the literature regarding PAPP-A values in pregnancies, the association between low values of PAPP-A MoM and maternal-fetal complications were investigated.What do the results of this study add? This study retrospectively examines the PAPP-A MoM levels and the occurence of RDS. In neonates that were delivered at or beyond 37 weeks of gestation, RDS occurrence could be predicted at a significant rate by utilising PAPP-A MoM values which was measured at the first trimester fetal anomaly screening test.What are the implications of these findings for clinical practice and/or further research? In the light of these findings, in order to reduce RDS related neonatal morbidity and mortality, pregnancies with PAPP-A MoM values greater than 1.02 at the first trimester fetal anomaly screening should be more closely followed up and a higher rate of suspicion should be kept for RDS occurrence.

The Impact of Assisted Reproduction on First Trimester Biochemical Markers in Singleton and Twin Pregnancies

The objective was to determine the effect of in vitro fertilization (IVF) on nuchal translucency, free beta-human chorionic gonadotropin (Free b-HCG) and pregnancy-associated plasma protein-A (Papp-A) measurements for singleton and twin pregnancies. This was a retrospective population-based register study that included 2921women with 11-13 weeks of gestation singleton and twin pregnancies. All patients were evaluated for the first trimester Down syndrome combined screening. We identify the effect of assisted reproductive technologies (ART) such as in vitro fertilization (IVF) on the nuchal translucency (NT), free beta-human chorionic gonadotropin (b-HCG) and pregnancy-associated plasma protein-A (PAPP-A) values. The study included 2921 patients: 2526 with spontaneous conception (86.5%) and 395 following IVF (13.5%); in our study singleton pregnancies were 2660 (91.1%), dichorionic twin pregnancies 232 (7.9%) and 12 (0.4%) monochorionic twin pregnancies. The mean b-HCG were about 56.67 IU/l (95%CI: 54.98-58.36) in singleton pregnancies and 128.08 IU/l (95%CI: 115.72-140.45) in twin pregnancies. PAPP-A mean values in singleton pregnancies were 3.54 IU/l (95%CI: 3.42-3.66) and 5.25 IU/l (95%CI: 4.46-6.08) in twin pregnancies. The results were statistically significant with p value p�01. There were also significant differences between b-HCG values in spontaneous pregnancies HCG 63.35 IU/l (95%CI: 60.14-64.10) and IVF pregnancies HCG 99.9 IU/l (95%CI: 91.8-107.99) with p value p � 0.01. In our study the IVF had no impact on nuchal translucency values. Free b-HCG levels were higher in twin pregnancies and IVF pregnancies. PAPP-A concentrations were exceeded in twin pregnancies.

Biomarkers of oxidative stress in pregnant women with recurrent miscarriages

Abstract Background The aim of this study was to evaluate the markers of oxidative stress (OS), as well as the magnesium (Mg) concentration, pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (β-hCG) values in patients with previous recurrent miscarriages, with the purpose of comparing the level of OS with normal pregnancy. Methods The study was conducted as a prospective study, which included a total of 95 pregnant women divided into two groups. In the study group (n = 35), there were women with at least three consecutive previous miscarriages. The control group (n = 60) consisted of healthy pregnant women without previous miscarriages and complications in pregnancy. Blood samples were taken between the 11th and 14th weeks of gestation, and the values of superoxide dismutase (SOD-1), glutathione peroxidase (GSH-Px) and total antioxidant status (TAS) in the serum, as well as the Mg concentration, PAPP-A and β-hCG values were determined. Results The values of SOD and GHS-Px were statistically higher in the study group, while the values of TAS were statistically significantly higher in the control group. The values of the Mg concentration were statistically significantly higher in the control group, while the values of β-hCG were statistically significantly higher in the study group. When the study group was divided into subgroups according to the outcome of pregnancy, there were statistical differences in the level of GSH-Px, SOD between miscarriages and the term delivery group, as well as in the Mg concentration between miscarriages and the term delivery group and between the term and preterm delivery groups. Higher values of SOD and GHS-Px, and lower values of TAS and Mg concentration could be used as markers for the prediction of spontaneous miscarriages. Conclusions The results of this research indicated higher OS and exhaustion of antioxidant mechanisms in early pregnancy in a group with recurrent miscarriages. Also, lower values of serum Mg concentration could be one of the markers for the prediction of spontaneous miscarriages.