PAPP-A Concentrations Research Articles

The influence of trophectoderm biopsy for preimplantation genetic testing in the serum level of first trimester biomarkers: PAPP-a, βhCG and PIGF

Research questionDoes trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first trimester pregnancy biomarkers (PAPP- A, free β-hCG, PlGF)? DesignRetrospective cohort study, including all singleton pregnancies (n=9794) following either spontaneous conceived (SC) (n=8005) in vitro fertilization and fresh embryo transfers (IVF) (n=478) or frozen embryo transfer of non PGT-A (FET)(n=963) or PGT-A tested embryos (FET+PGT-A) (n=348). In all women with a viable pregnancy at 8-13.6 weeks of pregnancy, we measured serum levels of free β-hCG and PAPP-A . PlGF was measured in 3784 patients. These biomarkers were converted to a multiple of the expected normal median (MoM) for a pregnancy of the same gestational day. We calculated the medians for the multiple of the median and compared them. ResultsFree β-hCG did not differ according to the mode of conception. PAPP-A concentrations were significantly lower in in vitro fertilization and fresh embryo transfers (-0,1 Log10 MoM raw PAPP-A) when comparing to FET+PGT-A (-0,04 Log 10 MoM raw PAPP-A) and SC (-0,0187 Log 10 MoM raw PAPP-A) (p<0,05). PlGF levels were significantly lower in the FET+PGTA group (p<0.05). The difference in means adjusted by CRL was 4.6 pg/ml 95%CI [2.7-6.6] for SC, 3.5 pg/ml 95%CI [0.34-6.6] for IVF and 2.2 pg/ml 95%CI [0.06-4.4] for FET. ConclusionThis study demonstrates that trophectoderm biopsy for PGT-A has a significant impact on first trimester maternal serum PAPP-A and PIGF. This needs to be further validated since it may mislead the estimation of the first trimester risk of aneuploidies and preeclampsia.

Prepubertal children with obesity have high free IGF-1 levels and accelerated growth despite reduced pappalysin levels.

Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation and changes in the GH-IGF axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity. We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1 and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system. Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls. Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I (fIGF-I), intact IGFBP-3, ALS, IGF-II and insulin levels, with no difference in the free/total IGF-I ratio. Neither the standardized BMI nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2 and PAPP-A were observed after weight loss. Increased circulating total and free IGF-I, insulin and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.

Study of biochemical markers during the first trimester of pregnancy among women of Almaty city

One of actual problems is the birth of children with genetic diseases, such as Down syndrome, Edwards syndrome, Patau syndrome, Shereshevsky-Turner syndrome. Study of level of biochemical markers of the first trimester of pregnancy for diagnose of chromosomal abnormalities in fetus was the purpose and objectives of this research. A risk group was identified, including 684 women on the base of results of studies of biochemical markers of the 1-st trimester of pregnancy – PAPP-A and β-hCG. In these pregnant women, PAPP-A and β-hCG concentrations were higher or lower than normal values. It has been shown that decrease in PAPP-A levels and increase or decrease in β-hCG in the 1-st trimester of pregnancy may indicate the presence of a chromosomal abnormality in the fetus. Next, a pattern has been identified that with increasing women age, the risk of having children with chromosomal abnormalities increases. During the study, it was found that PAPP-A levels are reduced at Down and Edwards syndromes and slightly reduced at Shereshevsky-Turner syndrome. Level of β-hCG is significantly higher at Down syndrome, while at Edwards syndrome, on the contrary, it has reduced values; and at Shereshevsky-Turner syndrome the level of β-hCG has a normal value. Changes in levels of these indicators from norm do not always indicate a fetal pathology, but they are grounds for further medical examination.

Increased IGFBP Proteolysis, IGF-I Bioavailability, and Pappalysin Levels in Children With Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is associated with impaired growth hormone (GH) secretion and decreased insulin-like growth factor (IGF)-I levels. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implication in PWS is unknown. We determined serum levels of PAPP-As and STCs in association with IGF axis components in prepubertal and pubertal patients with PWS, also analyzing the effect of GH treatment. Forty children and adolescents with PWS and 120 sex- and age-matched controls were included. The effect of GH was evaluated at 6 months of treatment in 11 children. Children with PWS had lower levels of total IGF-I, total and intact IGFBP-3, acid-labile subunit, intact IGFBP-4, and STC-1, and they had higher concentrations of free IGF-I, IGFBP-5, and PAPP-A. Patients with PWS after pubertal onset had decreased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4 levels, and had increased total IGFBP-4, and STCs concentrations. GH treatment increased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4, with no changes in PAPP-As, STCs, and free IGF-I levels. Standardized height correlated directly with intact IGFBP-3 and inversely with PAPP-As and the free/total IGF-I ratio. The increase in PAPP-A could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability in children with PWS. Further studies are needed to establish the relationship between growth, GH resistance, and changes in the IGF axis during development and after GH treatment in these patients.

Further Evidence that an Episode of Premature Labor Is a Pathologic State: Involvement of the Insulin-Like Growth Factor System

Introduction: Approximately 47% of women with an episode of preterm labor deliver at term; however, their infants are at greater risk of being small for gestational age and for neurodevelopmental disorders. In these cases, a pathologic insult may disrupt the homeostatic responses sustaining pregnancy. We tested the hypothesis of an involvement of components of the insulin-like growth factor (IGF) system. Methods: This is a cross-sectional study in which maternal plasma concentrations of pregnancy-associated plasma protease (PAPP)-A, PAPP-A2, insulin-like growth factor-binding protein 1 (IGFBP-1), and IGFBP-4 were determined in the following groups of women: (1) no episodes of preterm labor, term delivery (controls, n = 100); (2) episode of preterm labor, term delivery (n = 50); (3) episode of preterm labor, preterm delivery (n = 100); (4) pregnant women at term not in labor (n = 61); and (5) pregnant women at term in labor (n = 61). Pairwise differences in maternal plasma concentrations of PAPP-A, PAPP-A2, IGFBP-1, and IGFBP-4 among study groups were assessed by fitting linear models on log-transformed data and included adjustment for relevant covariates. Significance of the group coefficient in the linear models was assessed via t-scores, with p < 0.05 deemed a significant result. Results: Compared to controls, (1) women with an episode of premature labor, regardless of a preterm or a term delivery, had higher mean plasma concentrations of PAPP-A2 and IGFBP-1 (each p < 0.05); (2) women with an episode of premature labor who delivered at term also had a higher mean concentration of PAPP-A (p < 0.05); and (3) acute histologic chorioamnionitis and spontaneous labor at term were not associated with significant changes in these analytes. Conclusion: An episode of preterm labor involves the IGF system, supporting the view that the premature activation of parturition is a pathologic state, even in those women who delivered at term.

The Levels of Pregnancy-Associated Plasma Protein (PAPP-A) and Chorionic Gonadotropin (β-hCG) in the Blood Serum of Women with Hypothyroidism in the 1st Trimester of Pregnancy.

Hypothyroidism occurs in pregnant women at a rate of 0.3% to 3%. The deficiency of thyroid hormones during pregnancy can lead to an increased risk of pregnancy complications and poor health of the child, particularly affecting its psychomotor development due to the intensive growth of the nervous system during gestation. The study attempted to establish the median concentrations of pregnancy-associated plasma protein PAPP-A and the free subunit of human chorionic gonadotropin β-hCG in women with hypothyroidism in the 1st trimester of pregnancy. The study attempted to establish the median concentrations of pregnancy-associated plasma protein PAPP-A and the free subunit of human chorionic gonadotropin β-hCG in women with hypothyroidism in the 1st trimester of pregnancy. The study included 210 pregnant women between 11 and 13.6 weeks of pregnancy; 105 women were diagnosed with hypothyroidism before or during pregnancy, and 105 women of a similar body weight and gestational age had normal thyroid function.The measurements of the pregnancy parameters studied were performed using the DELFIA® Xpress system. Differences in the multiples of the median of the PAPP-A and β-hCG levels between women with hypothyroidism and healthy women were observed. Introducing correction for patients with hypothyroidism during non-invasive biochemical prenatal testing may allow obtaining more reliable results that would be the basis for referral to invasive procedures.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening

IntroductionExtreme levels of either PAPP-A or free β-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. MethodsA total number of 8591 patients with singleton pregnancies between 11 + 0–13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free β-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. ResultsValues of PAPP-A ≥ 2,0 MoM and free β-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free β-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free β-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free β-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free β-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DiscussionPregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free β-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free β-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

First-Trimester Biochemical Serum Markers in Female Kidney Transplant Recipients-The Impact of Graft Function.

Data on serum biochemistry markers as a component of the first-trimester screening test in pregnant kidney graft recipients are limited. In the absence of a separate validated algorithm, biochemical testing is commonly used in the first-trimester screening in kidney transplant recipients. Therefore, the study aimed to analyze first-trimester serum biochemical markers and the first trimester combined screening results in pregnant kidney graft recipients. A retrospective study was carried out in pregnant women who underwent the first-trimester combined screening test performed per the Fetal Medicine Foundation (FMF) protocol in 2009−2020. The study group included 27 pregnancies in kidney graft transplant recipients, and the control group was 110 patients with normal kidney function, matched according to age, body mass index (BMI), and gestational age. The biochemical serum markers (free beta-human chorionic gonadotropin [beta-hCG] and pregnancy-associated plasma protein A [PAPP-A]) were evaluated using the FMF-approved Roche Elecsys® assay and exhibited as multiples of the median (MoM) values. Data on first-trimester screening test results, perinatal outcomes, and graft function (assessed using serum creatinine concentrations) were analyzed. The analysis of first-trimester screening parameters revealed no difference in nuchal translucency (NT) measurements and uterine artery flow. However, free beta-hCG MoM and PAPP-A values were higher in posttransplant pregnancies than in controls: 3.47 ± 2.08 vs. 1.38 ± 0.85 (p = 0.035) and 1.46 ± 0.81 vs. 0.98 ± 0.57 (p = 0.007), respectively. The false positive rate of trisomy 21 (T21) screening in graft recipients was 25.9% vs. 3% in the controls. The free β-hCG MoM values positively correlated with serum creatinine levels before (r = 0.653; p < 0.001), during (r = 0.619; p = 0.001), and after pregnancy (r = 0.697; p < 0.001). There was a statistically significant negative correlation for PAPP-A MoM values for postpartum serum creatinine concentration (r = −0.424, p = 0.035). Our results show significantly higher serum concentrations of free beta-hCG and PAPP-A in posttransplant pregnancies than in healthy controls, confirmed when exhibited as MoM values and their association with graft function was assessed by serum creatinine concentration. Taking those changes into account would reduce the high number of false positive test results in this group. The validated first-trimester screening algorithm that considers altered kidney function in pregnant kidney graft recipients remains to be developed.

Pappalysins and Stanniocalcins and Their Relationship With the Peripheral IGF Axis in Newborns and During Development.

Pappalysins (PAPP-A, PAPP-A2) modulate body growth by increasing insulin-like growth factor I (IGF-I) bioavailability through cleavage of insulin-like growth factor binding proteins (IGFBPs) and are inhibited by stanniocalcins (STC1, STC2). Normative data on these novel factors, as well as on free IGF-I and uncleaved fractions of IGFBPs, are not well established. This work aimed to determine serum concentrations of PAPP-A, PAPP-A2, STC1, and STC2 in relationship with other growth hormone (GH)-IGF axis parameters during development. Full-term newborns (150; gestational age: 39.30 ± 1.10 weeks), 40 preterm newborns (30.87 ± 3.35 weeks), and 1071 healthy individuals (aged 1-30 years) were included in the study and divided according to their Tanner stages (males and females): I:163 males, 154 females; II:100 males, 75 females; III:83 males, 96 females; IV: 77 males, 86 females; and V:109 males,128 females. Serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were elevated at birth and declined throughout childhood. In postnatal life, PAPP-A2 concentrations decreased progressively in concomitance with the free/total IGF-I ratio; however, stanniocalcin concentrations remained stable. PAPP-A2 concentrations positively correlated with the free/total IGF-I ratio (r = +0.28; P < .001) and negatively with the intact/total IGFBP-3 ratio (r = -0.23; P < .001). PAPP-A concentrations inversely correlated with intact/total IGFBP-4 ratio (r = -0.21; P < .001), with PAPP-A concentrations being lower in females at all ages. Association studies indicate the importance of stanniocalcins and pappalysins in the control of this axis in an age-specific manner. This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of cleaved and uncleaved IGFBPs.

Metabolic improvement after gastric bypass correlates with changes in IGF-regulatory proteins stanniocalcin-2 and IGFBP-4

BackgroundPregnancy-associated plasma protein-A (PAPP-A) is an enzyme that increases IGF-activity through cleavage of IGF-binding proteins (IGFBPs), primarily IGFBP-4, whereby bound IGF-I becomes released as a free molecule. The enzymatic activity of PAPP-A is irreversibly suppressed by the glycoprotein stanniocalcin-2 (STC2). Pre-clinical and clinical studies suggest that the STC2 – PAPP-A – IGFBP-4 axis is important in controlling local IGF-action. STC2, PAPP-A and IGFBP-4 are expressed in adipose tissue, and as bariatric surgery markedly reduces the amount of fat, we found it relevant to study the impact of Roux-en-Y gastric bypass (RYGB) on circulating concentrations of this IGF-regulatory network. MethodsAnalysis of fasting blood samples from 20 obese subjects, hereof 10 with preoperative type 2 diabetes, investigated before RYGB, and 1 week, 3 months and 12 months post-surgery. Members of the IGF-system were analyzed by immunoassays, bioactive IGF by cell-based IGF-I receptor activation assay. We compared changes in IGF-system components with changes in fasting plasma insulin and glucose, and HbA1c. ResultsPAPP-A remained unchanged, but STC2 decreased following RYGB (p < 0.05). The PAPP-A substrate IGFBP-4 declined (p < 0.01), whereas levels of PAPP-A specific IGFBP-4 fragments increased (p < 0.05), indicating an increased PAPP-A enzymatic activity post-RYGB. Further, the reduction in intact IGFBP-4 correlated with increased levels of bioactive IGF (p < 0.05). In multivariable regression analyses, an improved glucose metabolism correlated with reductions in STC2 and IGFBP-4, and with increases in bioactive IGF and IGF-I (p < 0.05). ConclusionAfter 12 months, RYGB caused reduced serum concentrations of intact IGFBP-4 and STC2, whereas serum PAPP-A remained at pre-operative levels. However, concentrations of PAPP-A generated IGFBP-4 fragments increased, pointing to an overall increased PAPP-A enzymatic activity following RYGB. Notably, reductions in intact IGFBP-4 and STC2 associated with improvements in glucose metabolism. Therefore, we propose that STC2 and IGFBP-4 are involved in the metabolic improvement that follows RYGB.

Evaluation of indications for amniocentesis in cases of normal fetal ultrasound results.

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. 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. 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. 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.

Both Low and High PAPP-A Concentrations in the First Trimester of Pregnancy Are Associated with Increased Risk of Delivery before 32 Weeks in Twin Gestation.

In twin gestation, the relationship between pregnancy associated plasma protein (PAPP-A) and perinatal outcome is unclear. The aim of the study was to determine if low and high concentrations of PAPP-A in the first trimester are related to perinatal outcome in twins. A retrospective study was conducted. Medical data of women in twin pregnancies who delivered between 2013 and 2018 were analyzed. PAPP-A concentrations were measured between 10 + 0 and 13 + 6 weeks. The associations between low (<10th percentile) and high (>90th percentile) values of PAPP-A and pregnancy complications were analyzed. A total of 304 patients were included. PAPP-A <10th percentile was associated with a high risk of preterm delivery (OR 6.14; 95% CI 2.1–18), delivery <34 weeks (OR 2.39; 95% CI 1.1–5.1) or <32 weeks (OR3.06; 95% CI 1.4–6.8). Significant relations between PAPP-A >90th percentile and delivery <34 weeks (OR4.09; 95% CI 1.8–9.1) or <32 weeks (OR 2.83; 95% CI 1.2–6.6) were found. PAPP-A >90th percentile was related to high risk of intrauterine fetal demise (OR 10; 95% CI 2.4–42.5). Both low and high PAPP-A concentrations seem to be related to pregnancy outcome. Further research is needed to investigate evaluation of risk of pregnancy complications according to PAPP-A concentrations as a continuous variable.

Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-A and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor.

BackgroundPregnancy-associated plasma protein-A and -A2 (PAPP-A and -A2) are principally expressed in placental trophoblasts and play a critical role in the regulation of fetal and placental growth. PAPP-A2 shares 45% amino acid similarity with PAPP-A. This study aimed to investigate the efficacy of real-time detection of PAPP-A and PAPP-A2 using a novel surface plasmon resonance (SPR) biosensor based on graphene oxide (GO).MethodsTraditional SPR and GO-based SPR chips were fabricated to measure PAPP-A and PAPP-A2 concentrations. We compared SPR response curves of PAPP-A and PAPP-A2 between traditional SPR and GO-SPR biosensors. We also performed interference tests and specificity analyses among PAPP-A, PAPP-A2, and mixed interference proteins.ResultsThe time to detect PAPP-A and PAPP-A2 was about 150 seconds with both traditional SPR and GO-SPR biosensors. Approximately double SPR angle shifts were noted with the GO-SPR biosensor compared to the traditional SPR biosensor at a PAPP-A and PAPP-A2 concentration of 5 μg/mL. The limit of detection of the GO-SPR biosensor was as low as 0.5 ng/mL for both PAPP-A and PAPP-A2. Interference testing revealed that almost all of the protein bonded on the GO-SPR biosensor with anti-PAPP-A from the mixture of proteins was PAPP-A, and that almost no other proteins were captured except for PAPP-A2. However, the SPR signal of PAPP-A2 (5.75 mdeg) was much smaller than that of PAPP-A (13.76 mdeg). Similar results were noted with anti-PAPP-A2, where almost all of the protein bonded on the GO-SPR biosensor was PAPP-A2. The SPR signal of PAPP-A (5.17 mdeg) was much smaller than that of PAPP-A2 (13.94 mdeg).ConclusionThe GO-SPR biosensor could distinguish PAPP-A and PAPP-A2 from various mixed interference proteins with high sensitivity and specificity. It could potentially be used to measure PAPP-A and PAPP-A2 in clinical blood samples during pregnancy.

Association between fertility treatments and early placentation markers

IntroductionPregnancies resulting from fertility treatments are at higher risk of placenta-mediated complications. Hence, we aimed to estimate the association between fertility treatment and levels of first-trimester markers of placentation. MethodsWe conducted a cohort study in an academic center from 03/2011 to 12/2014. Adult nulliparous women with singleton pregnancies were recruited between 11 + 0 and 13 + 6 weeks of gestation. Data on maternal characteristics, medical history, and pregnancies conceived through fertility treatments (whether ovulation agents, insemination or assisted reproductive technologies) were collected. Maternal serum concentrations of PlGF, sFlt-1, PAPP-A, AFP, and free β-hCG were obtained, and notches and UtA-PI were measured using Doppler ultrasound. Mean Multiple of the Medians (MoM) and frequencies were computed to estimate the mean differences (MD) or risk ratios (RR) comparing fertility treatment to spontaneous pregnancies. Results427 (9%) pregnancies out of 4815 were conceived through fertility treatments, using ovulation agents (n = 233, 5%), insemination (n = 174, 4%) and/or assisted reproductive technologies (n = 85, 2%). The latter were associated with significantly lower log10PAPP-A MoM (adjusted MD: −0.02, 95%CI: −0.04 to −0.01), lower log10PlGF MoM (adjusted MD: −0.04, 95%CI: −0.06 to −0.01) and higher log10free β-hCG MoM (adjusted MD: 0.05, 95%CI: 0.01 to 0.09) compared to spontaneous pregnancies. Ovulation agents and insemination were associated with the presence of notches (adjusted RR: 1.24, 95%CI: 1.14 to 1.35; and 1.27, 95%CI: 1.15 to 1.42, respectively) and higher log10UtA-PI MoM (adjusted MD: 0.16, 95%CI: 0.08 to 0.24; and 0.17, 95%CI: 0.07 to 0.27, respectively) than spontaneous pregnancies. ConclusionFertility treatments are associated with significant variations in markers of placentation.

Influence of Weight of Pregnant Women on First Trimester Biochemical Markers Values

Values of first trimester biochemical markers (PAPP-A and free b-hCG) concentration are included in aneuploidies risk evaluation algorithm. Since both markers are produced by the fetus and placenta their concentration depends on the volume in which they are dissolved, respectively the weight of the pregnant women. Our study aimed to analyze the influence of maternal weight on first trimester biochemical markers concentration and the ability of the risk calculation software to correct this influence. Pregnancy-associated protein A (PAPP-A) and free � chorionic gonadotropin hormone (free � hCG) first trimester sera concentration respectively weight were measured in 1629 pregnant women. First trimester PAPP-A and free beta hCG concentrations inverse correlate with weight of pregnant women rho=-0.33, p[0.0001, respectively rho=-0.18, p[0.0001. Weight of pregnant women inversely correlates with multiple of median (MoM) values of first trimester markers too: rho=-0.38, p[0.0001 (PAPP-A), respectively rho=-0.17, p[0.0001 (free-b-hCG). The software counterbalances the influence of weight on biochemical markers values. PAPP-A corrected MoM (MoMc) values don�t inversely correlate with the weight (rho=-0.03, p=0.12), whereas free � hCG MoMc values showed an extremely weak inverse correlation (rho=-0.08, p=0.0008). The software counterbalances the influence of weight on PAPP-A values, whereas an extremely weak but insignificant inverse correlation between weight and free-beta hCG values persists after correction.

Nuchal translucency measurement, freeβ-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0 MoM) were performed. Free beta-human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR=1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR=1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR=1.00, 95%CI: 0.94-1.08 and RR=1.01, 95%CI: 0.97-1.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies. © 2017 John Wiley & Sons, Ltd.

PROGNOSIS OF ONE-DAY MORTALITY AND PROTEIN GROWTH AND DAMAGE FACTORS IN ACUTE CORONARY SYNDROME

Aim. To perform comparative analysis of the pregnancy-associated plasma protein A and insulin-like growth factor 1 (PAPP-A and IGF-1) in blood plasma of patients with acute coronary syndrome (ACS). Prediction of 24-hour risk of fatal outcome in ACS. Material and methods. The concentrations of PAPP-A and IGF-I were assessed in 71 ACS patients, mean age 57 y. o. In the study group, during 24 hours myocardial infarction (MI) was diagnosed in 44, unstable angina in 27, and 9 fatal outcomes. Also, the concentrations of PAPP-A and IGF-I were measured in comparison and control groups. Comparison consisted of 40 hypertension patients with stable ischemic heart disease. Controls were 20 almost healthy persons. Results. In the study, there was increase of PAPP-A and IGF-I levels in ACS patients. In unstable angina patients PAPP-A is higher than in controls 3,56 times, and in MI patients 11,6 times. In MI, PAPP-A is 3,2 times higher than in unstable angina. In unstable angina patients there the highest levels of IGF-I, and 1,27 higher than in controls. In the study, we showed that IGF-I and PAPP-A levels in acute coronary pathology are linked to the outcome at the first day of the disease. Conclusion. It is aim full to apply PAPP-A and IGF-I to urgent cardiology practice as an analyzer of atherosclerotic plaque instability in acute coronary events, as a factor of life and disease prognosis.

Pregnancy Associated Plasma Protein-A and Placental Growth Factor in a Sub-Saharan African Population: A Nested Cross-Sectional Study.

BackgroundBaseline distributions of pregnancy disorders’ biomarkers PlGF and PAPP-A levels are primarily based on Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated.ObjectivesTo investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF.MethodsA nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56–97 days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively.ResultsThe PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups.ConclusionsPAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes.

72 Pregnancy associated plasma protein-A and placental growth factor in a sub-Saharan African population: A nested cross-sectional study

Background Baseline distributions of pregnancy disorders' biomarkers PlGF and PAPP-A levels are primarily based on Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated. Objectives To investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF. Methods A nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56 and 97days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively. Results The PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Correlation between PAPP-A and PlGF MoM values was 0.21. Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups. Conclusions PAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes.

ОЦІНКА ПОКАЗНИКІВ СПЕЦИФІЧНИХ БІЛКІВ ВАГІТНОСТІ ТА ДИНАМІКА ЇХ РІВНЯ В СИРОВАТЦІ КРОВІ У ВАГІТНИХ ІЗ ЛОКАЛЬНИМ НЕПРОГРЕСУЮЧИМ ВІДШАРУВАННЯМ ХОРІОН А ТА ПЛАЦЕНТИ.

&lt;p&gt; Існують повідомлення щодо певної діагностичної цінності специфічних білків плаценти як материнської, так і плодової її частини, що дозволяють всебічно оцінити взаємовідносини у фетоплацентарному комплексі. Було обстежено 120 жінок з епізодами відшарування плаценти в анамнезі або діагностованими ретрохоріальними та ретроплацентарними гематомами при даній вагітності, які входили в групу ризику щодо невиношування вагітності. Контрольну групу склали 30 жінок з неускладненим перебігом вагітності. Оцінювали рівень специфічних білків вагітності (вільного естріолу, хоріонічного гонадотропіну та РАРР-А) в сироватці крові пацієнток з&lt;br /&gt;фізіологічною вагітністю та вагітністю, яка ускладнилася локальним непрогресуючим відшаруванням хоріона та плаценти, та їх коливання протягом першої половини гестаційного періоду. Що стосується концентрації білка вагітності РАРР-А в крові вагітних досліджуваних груп, варто відмітити у терміни 8–9 тижнів вагітності у 48,5 % пацієнток підвищення його вмісту&lt;br /&gt;майже вдвічі порівняно з контролем. Отримані результати дозволяють трактувати, що фізіологічному перебігу вагітності властиві односпрямовані зміни даних маркерів: низьким концентраціям РАРР-А відповідають низькі рівні β-ХГЛ, у той час як високі рівні РАРР-А супроводжуються підвищеним вмістом β-ХГЛ і тільки різноспрямовані зміни, насамперед РАРР-А та&lt;br /&gt;β-ХГЛ, дозволяють прогнозувати ускладнений перебіг вагітності.&lt;/p&gt;