Search

Objectives: The objective of this study was to analyze indications for amniocentesis in cases of patients with normal fetal ultrasound results between 11+0 and 13+6 weeks of gestation., Material and Methods: The results of first-trimester screening tests performed between 2014 and 2018 on 6,863 patients of the Prenatal Testing Outpatient Clinic at the Clinical Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland, were analyzed. The inclusion criteria were a singleton pregnancy and normal results of fetal ultrasound between 11+0- and 13+6-weeks' gestation. Depending on the calculated risk of fetal trisomy 21, the patients were divided into three groups (group A = RS > 1:300, group B = RS 1:300 - 1:999, group C = RS ≤ 1:1000). Subsequently, values such as PAPP-A and fβ-hCG protein levels and maternal age were analyzed for each of the groups., Results: The patients, 6,310 (91.94%) met the inclusion criteria. A high risk of fetal trisomy 21 was identified for 514 women (8.15%). Group B had 733 (11.62%) and group C 5,063 (80.23%) patients. In group A, an fβ-hCG level of ≥ 2.000 MoM was shown for 50.97% of the women. A PAPP-A level ranging from 0.001 to 0.499 MoM was observed for 38.72% of group A patients. The mean maternal age in groups A, B and C was 36.45, 36.08 and 31.64 years, respectively., Conclusions: In the first-trimester, patients with normal ultrasound results obtained during prenatal screening tests, the main cause of an increased risk of trisomy 21 was elevated PAPP-A and fβ-hCG concentrations. According to this paper's authors, in these cases extension of diagnosis to include other gestational complications, e.g. preeclampsia, should be considered.

Introductıon: PAPP-A (Pregnancy-associated plasma protein-A) is considered a pro-inflammatory marker and its serum levels are elevated in non-pregnant patients with asthma. In the current research, we aimed to investigate whether maternal serum PAPP-A levels, a biomarker for first-trimester aneuploidy screening, differ in pregnant women with asthma compared to healthy pregnant women. Methods: In the first step, maternal serum PAPP-A MoM values, used as the first-trimester fetal aneuploidy screening marker, were compared between pregnant women with asthma and a healthy pregnant group. In the second step, the groups compared whether PAPP-A and fβ-HCG ( free β human chorionic gonadotropin) levels were below or above the cut-off values for Trisomy 21 and compared them according to maternal age (<35; ≥35). Results: The median PAPP-A level was found to be 2.15 IU/L (0.41-9.91) in the asthma group and 2.54 IU/L (0.56-11.40) in the control group, and there was no difference between the groups (P=0.363). The median PAPP-A MoM value was 0.99 (0.15-3.28) in the asthma group and 1.07 (0.33-3.37) in the control group. This result did not show a statistically significant difference (P = 0.694). No statistically significant difference was shown between the groups below and above 35 age (P=0.456). Conclusion: Maternal serum PAPP-A levels in pregnant women with asthma do not vary compared to the healthy pregnant group without asthma. Based on the results of our study, the first-trimester fetal aneuploidy screening test is a reliable screening method for pregnant women with asthma. [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]

Background: Pregnancy Associated Placental Protein-A (PAPP-A) is a zinc-binding metalloproteinase with a key role in the insulin-like growth factor (IGF) pathway. The IGF system plays an essential role in follicular development, including steroid hormone synthesis, growth, recruitment, and apoptosis of follicles of women undergoing intracytoplasmic sperm injection (ICSI). Objective: The objective of this study is to measure Pregnancy Associated Plasma Protein-A (PAPP-A) in serum of infertile women undergoing ICSI, and to investigate the association of PAPP-A with some reproductive hormones level. A total of 45 infertile women. Results: The results of this study was Serum PAPP-A level was not significant with hormones level (FSH, LH PRO and AMH) except E2 hormone was significant. Conclusion: Outcome show that no relation between studied reproductive hormones and serum PAPP-A except E2 levels that are high cause the egg to mature and release from the ovary. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of vaginal birth complications with first trimester pregnancy associated plasma protein A (PaPP-A) level in LGA vaginal deliveries of non-diabetic mothers. Methods: This is a retrospective study conducted in a tertiary hospital between May 2020 and July 2022. A total of 9,184 singleton pregnancies with normal vaginal delivery between 37 and 42 weeks were reviewed. Non-diabetic patients who gave birth to LGA infants were grouped according to the presence of vaginal birth complications and compared in terms of first trimester aneuploidy screening results. Regression analysis was used to investigate the effect of variables on complications. Receiver operating characteristic (ROC) analysis was performed for the threshold PaPP-A value to predict birth complications. Results: Of the 357 patients, 68 (19.0%) had at least one complication, remaining 289 (81.0%) had no complications. First trimester serum PaPP-A level was significantly higher in complicated group than patients without complications (20.85 ± 19.73 vs 15.18 ± 15.81, p= 0.046). First trimester NT, β-hCG and PaPP-A are significantly associated with perinatal complications in LGA vaginal deliveries. The cut-off value of first trimester PaPP-A level was 10.46 mIU/mL to predict the complications with a sensitivity of 54.4% and a specificity of 54.3%. Conclusions: First trimester PaPP-A level may be associated with vaginal birth complications in LGA infants from non-diabetic mothers. [ABSTRACT FROM AUTHOR]

Aim: to find out the predictive value of blood serum biochemical parameters PAPP-A (pregnancy-associated plasma protein A) and β-hCG (beta subunit of human chorionic gonadotropin) in the assessment of unfavorable pregnancy outcomes in women infected by human immunodeficiency virus (HIV) as well as viral hepatitis B (HBV) and C (HCV).Materials and Methods. A retrospective study of the medical records from 52 women was carried out, including 19 HIV-infected women, 9 women with monoinfection HBV or HCV, 11 pregnant women who were co-infected (HIV/HBV or HIV/HCV) and 13 uninfected women. PAPP-A and β-hCG levels, expressed as MoM (multiple of median), were evaluated in all women.Results. Our study revealed that only PAPP-A was prognostically significant for developing chronic placental insufficiency in women with HIV infection and co-infection of HIV together hepatitis B and C. None of the parameters examined were significant in women with HBV or HCV monoinfection. PAPP-A and β-hCG in pregnant women without infections were effective in predicting development of chronic placental insufficiency.Conclusion. PAPP-A can be used as a diagnostic parameter of developing chronic placental insufficiency in pregnant women with monoinfection HIV and co-infection with HIV/HBV or HIV/HCV.

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 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. Methods: 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. Results: 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. Conclusions: 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 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening. Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex). Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (β = 0.147, 95% CI = [0.067–0.227] for protease inhibitor-based ART and β = 0.176, 95% CI = [0.080–0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure. Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP. [ABSTRACT FROM AUTHOR]

Objectives: To develop a continuous likelihood model for pregnancy-associated plasma protein-A (PAPP-A), in the context of a new competing-risks model for prediction of a small-for-gestational-age (SGA) neonate, and to compare the predictive performance of the new model for SGA to that of previous methods.Methods: 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. The dataset was divided randomly into a training dataset and a test dataset. The training dataset was used for PAPP-A likelihood model development. We used Bayes' theorem to combine the previously developed prior model for the joint Gaussian distribution of gestational age (GA) at delivery and birth-weight Z-score with the PAPP-A likelihood to obtain a posterior distribution. This patient-specific posterior joint Gaussian distribution of GA at delivery and birth-weight Z-score allows risk calculation for SGA defined in terms of different birth-weight percentiles and GA. The new model was validated internally in the test dataset and we compared its predictive performance to that of the risk-scoring system of the UK National Institute for Health and Care Excellence (NICE) and that of logistic regression models for different SGA definitions.Results: PAPP-A has a continuous association with both birth-weight Z-score and GA at delivery according to a folded-plane regression. The new model, with the addition of PAPP-A, was equal or superior to several logistic regression models. The new model performed well in terms of risk calibration and consistency across different GAs and birth-weight percentiles. In the test dataset, at a false-positive rate of about 30% using the criteria defined by NICE, the new model predicted 62.7%, 66.5%, 68.1% and 75.3% of cases of a SGA neonate with birth weight < 10th percentile delivered at < 42, < 37, < 34 and < 30 weeks' gestation, respectively, which were significantly higher than the respective values of 46.7%, 55.0%, 55.9% and 52.8% achieved by application of the NICE guidelines.Conclusions: Using Bayes' theorem to combine PAPP-A measurement data with maternal characteristics improves the prediction of SGA and performs better than logistic regression or NICE guidelines, in the context of a new competing-risks model for the joint distribution of birth-weight Z-score and GA at delivery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [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]

Background. During the late first trimester, between 11-13 weeks of gestation, it is recommended for all pregnant women to have a screening for Down syndrome and for other chromosomal abnormalities like trisomy 13 or 18, because it estimates the potential risk and allows patients to make an informed choice about the continuation of pregnancy. The combined test analyzes three markers along with the maternal age: maternal serum beta-human chorionic gonadotropin (beta-hCG or free beta-hCG subunit), maternal serum pregnancy-associated plasma protein-A (PAPP-A) and an ultrasound measurement of nuchal translucency (NT). Objectives. To determine if there are differences regarding serum markers and pregnancy outcomes between spontaneous pregnancies and pregnancies obtained by assisted reproductive techniques (ART). Materials and method. We performed a literature review by searching MEDLINE and Cochrane databases using the keywords: beta-hCG, PAPP-A, screening, IVF, ICSI, ART, implantation. Results. Assisted reproduction techniques, such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), can alter serum markers levels and mimic the pattern associated with Down syndrome: maternal serum beta-hCG and inhibin A levels tend to be increased, while estradiol and PAPP-A levels are decreased. When comparing spontaneously conceived (SC) singleton pregnancies with in vitro fertilization/intracytoplasmic sperm injection, cohort studies confirm an increased risk of perinatal complications for the latter. The most frequent adverse outcomes are: preterm birth, intrauterine growth restriction, perinatal mortality, congenital malformations and higher risks for preeclampsia and placenta praevia. Conclusions. Overall, the risk of complications is significantly higher in ART pregnancies, but the reasons for this increase are still uncertain. The possible cause of this difference might be the increased maternal age and the particularities that occur during the implantation and placentation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening.Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex).Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (β = 0.147, 95% CI = [0.067-0.227] for protease inhibitor-based ART and β = 0.176, 95% CI = [0.080-0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure.Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP. [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]

Familial Mediterranean Fever (FMF) is the most common hereditary monogenic auto-inflammatory disease. In this study we aimed to document whether FMF affects the biochemical components of first and second trimester combined aneuploidy screening tests including serum free beta human chorionic gonadotropin (β-hCG), placenta associated plasma protein-A (PAPP-A), unconjugated estriol (uE3), total hCG and alfa-fetoprotein (AFP). In this prospective case control study, a total of consecutive 59 singleton pregnancies, 29 of with FMF and other 30 healthy women, were followed from the first trimester to end of the pregnancy. Most of pregnant women with FMF (86.2%) were under treatment with colchicine. The markers PAPP-A, free β-hCG and the nuchal translucency (NT) thickness were examined at 11-13 weeks. Serum samples for AFP, uE3 and total hCG were obtained at 16-19 weeks after detailed examination. There were no cases of fetal chromosomal anomaly in neither of the groups. Both first-and second trimester marker levels were not significantly different in absence of aneuploidy or neural tube defects in FMF and control group. No difference was seen for NT measurements. False-positive rate for Down syndrome was comparable between the groups using a term risk cut-off level of 1/250. Pregnant with FMF should be reassured about the not altered levels of first-and second trimester marker. Therefore readjusting the serum markers used for Down syndrome screening is not advised. Future trials of larger scale are needed to assess any need for readjustment of the risk in the patient population with FMF. [Med-Science 2016; 5(2.000): 448-56]

Objective: To evaluate the relationship between maternal serum levels of pregnancy-associated-plasma-protein-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.

Aims: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy.Methods: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy.Results: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10−4; quadratic term: p = 1.0 × 10−3; n = 889; overall model p = 8.1 × 10−3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = −0.13, p = 5.2 × 10−4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = −0.11, p = 2.8 × 10−3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771).Conclusions: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance. [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]

Background: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2) can be detected in serum of HD patients and to define its significance. Methods: The studied group consisted of 102 long-term HD patients and 25 healthy controls. HD patients were prospectively followed up for five years (2009-2014). PAPP-A2 was measured by surface plasmon resonance biosensor, PAPP-A by time resolved amplified cryptate emission. Results: PAPP-A2, similarly as PAPP-A, was significantly increased in HD patients (median (interquartile range)) PAPP-A2: 6.2 (2.6- 10.8) ng/mL, vs. 3.0 (0.7-5.9) ng/mL, p=0.006; PAPP-A: 18.9 (14.3-23.4) mIU/L, vs. 9.5 (8.4-10.5) mIU/L, p<0.001). In HD patients, PAPP-A2 correlated weakly but significantly with PAPP-A (τ=0.193, p=0.004). Unlike PAPP-A, PAPP-A2 was not significant for prognosis of HD patients when tested alone. There was a significant interaction between PAPP-A and PAPP-A2 on the mortality due to infection of HD patients (p=0.008). If PAPP-A was below median, mortality due to infection was significantly higher for patients with PAPP-A2 values above median than for patients with low PAPP-A2 levels (p=0.011). Conclusion: PAPP-A2 is increased in HD patients and interacts with PAPP-A on patient's prognosis. [ABSTRACT FROM AUTHOR]

Objective: Investigating potential value of maternal serum Visfatin, sFlt-1, PlGF, AFP, PAPP-A levels at first trimester for prediction of small for gestational age (SGA) at birth.Methods: Measurements were performed in 20 SGA and 65 control cases. Logistic regression analysis adjusted for age and weeks of pregnancy at data collection was performed to estimate odds ratios (OR), 95% confidence intervals (95% CI) and p values separately for each potential predictor. A multiple regression model was used to assess the impact of all the promising predictors adjusted for each other. Receiver operating characteristic (ROC) analysis was used to indicate the ability to discriminate between SGA cases and controls.Results: There was an association of serum PlGF levels (OR 0.53 per interquartile range [IQR] increase in PlGF; 95% CI 0.24-1.16), sFlt-1/PlGF ratio (OR 1.42 per IQR increase in sFlt-1/PlGF; 95% CI 1.03-1.96), serum Visfatin levels (OR 0.31 per IQR increase in Visfatin; 95% CI 0.10-0.95) and smoking (OR 4.24; 95% CI 1.10-16.37) with SGA at birth.Conclusions: Associations between SGA and lower PlGF, Visfatin levels as well as increased sFlt-1/PlGF ratio and smoking status were detected which may contribute to predict SGA. [ABSTRACT FROM AUTHOR]

Objective: To determine the predictive value of biochemical markers, uterine artery Doppler, and maternal factors in predicting early-onset (EO) and late-onset (LO) pregnancy hypertension.Methodology: All singleton pregnancies between 11 and 13 weeks and 6 days gestation underwent estimation of body mass index (BMI), mean arterial pressure (MAP), uterine artery Doppler pulsatality index (PI, and resistance index), biomarker PAPP-A, and free β-hCG. Women who developed hypertension were treated as cases and normotensives were taken as controls. The cases were further divided into EO and LO hypertension. The comparison was undertaken by appropriate statistical analysis.Results: Pregnancy hypertension was seen in 399 (13.2%) women. EO hypertension was seen in 153 (38.3%), whereas LO was observed in 246 (61.7%). The significant markers for predicting hypertension in pregnancy were maternal age, BMI, MAP, uterine artery Doppler PI, and PAPP-A. A combination of MAP and BMI was a better predictor (sensitivity and specificity 80% and 52%, respectively) than PAPP-A and Doppler combined (sensitivity and specificity 62% and 52%, respectively). When all the above markers were combined, the sensitivity and specificity of the test was 73% and 70%, respectively. EO hypertension was better predicted compared with LO. The negative predictive value (NPV) of the test was above 90%, suggesting that if a woman had the marker below the cutoff, there was more than 90% chance that she would not develop hypertension later in pregnancy.Conclusion: A combination of variables increased the sensitivity and specificity of the test for hypertension in pregnancy. The markers examined were a predictor of EO hypertension, with a high NPV, making it a good screening test. [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]

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter 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.)

Background: An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation. Objective: To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n = 20), and their controls matched for parity, and maternal and gestational age. Method: Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay. Results: Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9 pg/mL, artery and vein, respectively, p < 0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0 ± 298.4 versus 690.3 ± 401.9 mIU/L, artery and vein, respectively, p < 0.05), and free β-hCG (mean: 33.9 ± 4.3 versus 17.2 ± 4.0 and 30.1 ± 5.2 versus 13.7 ± 3.3 ng/mL, artery, and vein respectively, p < 0.05). Conclusion: Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard. [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: The purpose of this study was to analyze the role of PAPP-A and placental volume measured between 11+0 and 13+6 weeks of gestation on the subsequent development of preeclampsia, and to determine the presence of any statistical difference. Methods: Placental volume and serum PAPP-A were measured on 740 pregnant women who referred to our hospital for routine care at 11+0 to 13+6 weeks of gestation. Antenatal care was successfully continued in 502 cases until delivery. Results: While 460 cases out of 502 cases who gave birth were not affected by preeclampsia, 18 of them were diagnosed with early preeclampsia before 34 weeks of gestation, and 24 of them with the late preeclampsia at or after 34 weeks of gestation as resulting with delivery. Mean placental volume was higher in the late preeclampsia group (p<0.01) and in the unaffected group (p<0.001) compared to the early preeclampsia group. There was no significant difference between the late preeclampsia group and the unaffected group in terms of the placental volume values. PAPP-A MoM values were higher in the late preeclampsia group (p<0.05) and the unaffected group (p<0.001) than the early preeclampsia group. There was no significant difference between the late preeclampsia group and the unaffected group in terms of the PAPP-A values. Conclusion: Mean PAPP-A and placental volume values were found significantly lower in preeclampsia group than unaffected group. Yet, it is difficult to provide prediction of preeclampsia only by using these two parameters according to the literature data. It may be helpful to obtain successful results for preeclampsia prediction by adding other factors associated with patient as well as PAPPA and placental volume findings. [ABSTRACT FROM AUTHOR]

Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. [ABSTRACT FROM AUTHOR]

Purpose: The corrections necessary to estimate the risk for Down syndrome in twin pregnancies have been pointed out. We performed a nested controlled study to evaluate the validity of these corrections in dichorionic twins conceived by IVF. Methods: Detailed clinical data was collected from the medical records. Twins were matched with a contemporaneous cohort of spontaneously conceived singleton pregnancies that serve as reference in a 1 to 4 ratio. All patients had their entire obstetrical care at our Hospital. The Student t-test was used for group comparisons and a p-value <0.05 was considered significant. Results: Nineteen sets of normal twins concordant in size and with appropriate weight for gestational age were matched with 80 normal and mature newborns. Significant differences between groups were found for maternal age, gestational age at delivery and newborn weight (all p < 0.01). No statistical differences were noted for the levels of the biochemical markers expressed as multiples of the median. However, a 15 % closer approximation to the laboratory median for PAPP-A and a 10 % closer approximation to the laboratory median for free β-hCG was evident in twins when compared to the reference group. Conclusions: These findings support the methods used to estimate the risk for Down syndrome in dichorionic twin pregnancies conceived after IVF. A future study with a larger sample size could confirm if the laboratory corrections done on the combined screening test improve the predictability of Down syndrome in dichorionic twin pregnancy conceived by IVF when compared to singleton pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To investigate if first trimester lipids, sonographic parameters and serum markers are related to small- and large-for-gestational age (SGA, LGA) infants. Methods: This study was conducted at Baskent University Adana Research Center between December 2009 and July 2011 and enrolled 433 women. Blood samples were drawn to measure fasting blood glucose, serum triglycerides, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, fβ-hCG and pregnancy associated protein-A (PAPP-A) at the first trimester. Crown rump length and nuchal translucency were measured as suggested by the fetal medicine foundation. Results: LGA group was significantly taller ( p = 0.016) and SGA group had significantly greater BMI (0.025). SGA fetuses were born at a significantly earlier gestational age ( p = 0.001). Univariate analysis revealed that LGA group had significantly lower cholesterol ( p = 0.038) and LDL levels ( p = 0.041). PAPP-A was significantly lower in SGA Group compared with LGA Group (0.027). After controlling for age, parity, height, pre-pregnant BMI, weight gain during pregnancy and fasting blood sugar, none of the lipids, serum markers or sonographic parameters was related to LGA. PAPP-A was the only parameter significantly associated with SGA after multivariate analysis ( p = 0.008). Conclusion: PAPP-A was significantly associated with SGA after controlling for confounders. [ABSTRACT FROM AUTHOR]

Objective: The serum pregnancy-associated plasma protein-A (PAPP-A) concentration is a predictor of ischemic cardiac events and renal impairment. However, the reference interval of PAPP-A has not been determined. This study determined the reference interval of PAPP-A in men and non-pregnant women. Methods: The study enrolled 126 apparently healthy individuals (52 males and 74 females). The mean age of the men and women was 34.7 (range 20-66) years and 34.6 (range 18-65) years, respectively. Serum PAPP-A concentrations were determined using an ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated using the bootstrap method. Results: The results for three subjects were outliers, so the reference interval of PAPP-A was calculated using the data for 123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of PAPP-A for men and women (with the 90% confidence interval) was <22.9ng/mL (19.7-23.3) and <33.6ng/mL (25.2-36.7), respectively. In male subjects, serum PAPP-A levels of smokers [3.10 (UD, 7.30)ng/mL] were significantly lower than that of non-smokers [ 11.00 (UD, 24.4) ng/mL) (p < 0.001 ) and there was a positive correlation between serum PAPP-A levels and subjects' age (r=0.439; p< 0.001). Conclusions: The reference interval of PAPP-A differed for men and non-pregnant women. In clinical practice, <22.9 ng/mL for men and <33.6 ng/mL for non-pregnant women may be used as reference intervals for PAPP-A. [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]