Pregnancy-associated Placental protein-A Research Articles

Concentration of maternal biochemical markers: Complications during pregnancy and their effect on the detection of trisomy 21 in the first trimester, by combined test (study carried out at a private clinic in CDMX)

Aneuploidies are alterations that affect the number of chromosomes. Historically, a combination of markers has been used that includes: maternal age, concentrations of biochemical markers and ultrasonographic markers during pregnancy, as well as screening in the first trimester in order to detect Trisomy 21 (T21).Objective:To identify if biochemical markers such as Pregnancy Associated Placental Protein A (PAPP-A) and Beta human Chorionic Gonadotropin (β-hCG) are altered by complications during pregnancy and if this leads to an increased risk of developing T21 in pregnant women with healthy babies (combined test).Material and method:Retrospective, observational and cross-sectional study, included 73 pregnant women. Anthropometric data from the mother and the newborn were collected. A combined test was performed in the 1st trimester and biochemical markers were recorded in maternal serum (β-hCG AND PAPP-A) and ultrasonographic markers [Nuchal Translucency (NT)]. In addition, the evaluation of Cell-Free Fetal DNA (cffDNA) in peripheral blood was performed to identify aneuploidies and a pathological study of the placenta.Results:In the group of patients with intermediate risk for T21, there was a higher prevalence of complications during pregnancy [fetal growth restriction (4.5%), preterm labor (4.5%), miscarriage (9.09%) and death (9.09%). In the same way, patients with intermediate risk presented a higher prevalence of placental alterations such as calcifications, atrophy, congested dilated vessels, hemorrhage, hematomas, Chorioangioma, extravasation of erythrocytes and villus infarcts.
 Conclusions:The development of placental alterations and the presence of complications in pregnancy could modify the peripheral blood concentrations of β-hCG and PAPP-A, and alter the results of the combined test for T21.

Serum pregnancy-associated placental protein-a (PAPP-A) levels are increased in polycystic ovary syndrome (PCOS) in women with oligo-anovulation

Background/Aim: Pregnancy associated placental protein-A (PAPP-A) is a zinc-binding metalloproteinase with a key role in insulin like growth factor (IGF) pathway, and potential atherogenic effects. There is little information in the literature regarding PAPP-A levels in Polycystic ovary syndrome (PCOS). We aimed to investigate the serum PAPP-A levels among non-obese women with PCOS as a cardiovascular risk marker. Methods: Non-obese women of reproductive age (18-35 years of age) diagnosed with PCOS according to Rotterdam Consensus Conference criteria were included in this case-control study. Serum PAPP-A levels were compared with independent samples t-test between two main groups (PCOS and control) and investigated in PCOS subgroups as PCOS patients were further classified according to main phenotypes (hyperandrogenism and oligo-anovulation). Results: A total of 41 women with PCOS and 40 age- and body mass index- matched controls were included in the analysis. The serum PAPP-A levels of the control and PCOS groups, and of PCOS patients with hyperandrogenism were similar (P=0.128, P=0.261, respectively). However, the serum PAPP-A levels of those with oligo-anovulation was higher than those without (P=0.006), and that of women without oligo-anovulation was comparable to that of the control group (P=0.613). Conclusion: Lean and young PCOS women with oligo-anovulation had increased serum levels of PAPP-A when compared to women without. Prospective studies are needed to uncover the long-term cardiovascular risk of elevated PAPP-A levels in PCOS women with oligo-anovulation.

Elevated PAPP-A levels in lean patients with polycystic ovary syndrome

ObjectivesThis study aimed to evaluate the serum concentrations of PAPP-A (pregnancy associated placental protein-A), a biomarker which is associated with cardiovascular disease, in patients with polycystic ovary syndrome (PCOS). Materials and MethodsA total of 62 women with PCOS, and 68 age and body mass index (BMI) matched controls were eligible for the study. Hirsutism scores, hormonal and metabolic profile as well as PAPP-A levels were assessed in each subject. ResultsWomen with PCOS and controls yielded similar median serum levels of PAPP-A (1.7 ng/ml versus 1.8 ng/ml, respectively, p = 0.328). However, when patients were compared based on BMI; subgroup analyses found that among women with BMI<27 kg/m2, patients with PCOS exhibited higher PAPP-A levels than controls (2.1 ng/ml versus 1.8 ng/ml, respectively, p = 0.018). When women with PCOS were evaluated in their own based on BMI, lean PCOS women showed higher levels of PAPP-A (2.1 ng/ml versus 1.5 ng/ml, p = 0.002). PAPP-A levels were negatively correlated with age (p = 0.031, r = −0.189), BMI (p = 0.002, r = −0.265) and triglyceride levels (p < 0.001, r = −0.3). ConclusionThe data of the present study suggested that PAPP-A might be a clinical indicator in PCOS, in which the risks of metabolic syndrome and cardiovascular event are increased. Especially a group of young patients with BMI <27 kg/m2 might benefit from the cardiovascular risk evaluation using PAPP-A, supplying prognostic information for high risk in the development of cardiovascular disease.

Low maternal pregnancy-associated plasma protein A during the first trimester of pregnancy and pregnancy outcomes.

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

Could first-trimester assessment of placental functions predict preeclampsia and intrauterine growth restriction? A prospective cohort study

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

First Trimester Placental Retinol-Binding Protein 4 (RBP4) and Pregnancy-Associated Placental Protein A (PAPP-A) in the Prediction of Early-Onset Severe Pre-Eclampsia

ObjectiveIn a retrospective case–control study, we examined the levels of placental retinol-binding protein 4 (RBP4) and pregnancy-associated placental protein A (PAPP-A) in first-trimester maternal serum samples as well as maternal characteristics to predict early-onset and severe pre-eclampsia. MethodsIn this retrospective case–control study, we identified females who delivered a singleton pregnancy on or after 24weeks’ gestation from 2003 to 2010 at Oulu University Hospital and had a retrospective first trimester trisomy screening, including serum PAPP-A measurement. Within this cohort, we identified 65 females who experienced early onset pre-eclampsia (EO-PE) and 742 controls who had uncomplicated deliveries. Retrospectively, we thawed all previously collected serum samples to measure placental retinol binding protein 4 (RBP4). PAPP-A and RBP4 were measured using automatic immunoassay systems and converted to multiples of the median (MoMs). Logistic regression analysis was performed to determine whether these biomarkers separately and in combination with maternal characteristics (maternal age, weight and smoking status) can be used to predict the development of early onset pre-eclampsia. ResultsThe expected log10 PAPP-A concentration and the expected log10 RBP4 concentration in the control group were both affected by maternal weight and smoking status. The expected log10 PAPP-A concentration was also affected by gestational age (GA). RBP4 levels in first-trimester serum were significantly higher in females who subsequently developed EO-PE outcome compared to those with normal pregnancy outcome (1.14 vs. 1.01 MoMs, p<0.0001). Maternal serum PAPP-A levels from the same pregnancy period were significantly lower in the EO-PE group compared to controls (0.80 vs. 1.05 MoMs, p=0.005). The risk model including maternal characteristics with PAPP-A log10 MoM and RBP4 log10 MoM had the best EO-PE prediction ability. It detected 34% (23%–46%) of females with subsequent EO-PE with a 10% false positive rate. ConclusionThis study showed that first-trimester maternal serum RBP4 was significantly increased and that PAPP-A decreased in pregnancies that ended in EO-PE compared to normal pregnancies. Thus, these markers may be useful members in a panel of markers for the early detection of early-onset and severe pre-eclampsia.

Pattern of secretion of pregnancy-associated plasma protein-A (PAPP-A) during pregnancies complicated by fetal aneuploidy, in vivo and in vitro.

BackgroundPregnancy-associated placental protein-A (PAPP-A) is a metalloprotease which circulates as an hetero-tetramer in maternal blood. Its maternal serum concentration in fetal trisomy 21 is decreased during the first trimester, so that PAPP-A is a useful screening biomarker. However, the regulation of PAPP-A placental secretion is unclear. We therefore investigated the secretion of PAPP-A in pregnancies complicated by fetal aneuploidies, both in vivo and in vitro.MethodsMaternal serum collected between 10 WG and 33 WG during 7014 normal pregnancies and 96 pregnancies complicated by fetal trisomy 21, 18, and 13 were assayed for PAPP-A using the Immulite 2000xpi system®. The pregnancies were monitored using ultrasound scanning, fetal karyotyping and placental analysis. Villous cytotrophoblasts were isolated from normal and trisomic placenta and cultured to investigate PAPP-A secretion in vitro (n = 6).ResultsAn increased nuchal translucency during the first trimester is a common feature of many chromosomal defect but each aneuploidy has its own syndromic pattern of abnormalities detectable at the prenatal ultrasound scanning and confirmed at the fetal examination thereafter. PAPP-A levels rise throughout normal pregnancy whereas in trisomy 21, PAPP-A levels were significantly decreased, but only during the first trimester. PAPP-A levels were decreased in trisomy 13 and sharply in trisomy 18, whatever the gestational age. In vitro, PAPP-A secretion was decreased in aneuploidy, and associated with decreased hCG secretion in Trisomy 21 and 18. These biochemical profiles did not appear to be linked to any specific histological lesions affecting the placenta.ConclusionsThese profiles may reflect different quantitative and qualitative placental dysfunctions in the context of these aneuploidies.

Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy

Objective: To evaluate first and second-trimester maternal serum markers in pregnancies complicated with inherited thrombophilias. Methods: A case-control study was conducted in 50 pregnancies complicated with hereditary thrombophilia and 100 control pregnancies. Results: Each woman with inherited thrombophilia received low molecular weight heparin (LMWH) throughout her pregnancy. Gravidity, parity, number of first-trimester and second-trimester abortions, and rate of adverse pregnancy outcomes (APO) were significantly higher in the thrombophilia group compared to the control group (P < 0.001 for all). Among the thrombophilia group median values of pregnancy associated placental protein-A (PAPP-A) (0.6 vs. 0.9; P < 0.001) and free β-human chorionic gonadotropin (β-hCG) (0.9 vs. 1.1; P = 0.001) in the first trimester; median values of α-fetoprotein (AFP) (0.7 vs. 1.1; P = 0.027), unconjugated estriol 3 (uE3) (0.9 vs. 1.1; P < 0.001), and hCG (0.7 vs. 1.2; P < 0.001) in the second trimester were significantly lower with respect to control pregnancies. Multivariate analysis revealed that low uE3 and hCG levels were independently associated with APO. Conclusion: Pregnant women with hereditary thrombophilias, all of whom were treated with LMWH, had decreased levels of all first and second trimester serum markers. In addition, levels of hCG and uE3 in the second trimester could independently predict placenta-related disorders and adverse outcomes in these patients.

Unfractionated heparin for second trimester placental insufficiency: a pilot randomized trial

To conduct a pilot randomized controlled trial of unfractionated heparin (UFH) in women considered at high risk of placental insufficiency in the second trimester. Women with either false-positive first trimester (pregnancy-associated placental protein-A [PAPP-A] < 0.35 MoM) or second trimester (alpha-fetoprotein [AFP] > 2.0 MoM, inhibin > 3.0 MoM, human chorionic gonadotropin > 4.0 MoM) serum screening tests or medical/obstetric risk factors were screened for placental insufficiency by sonographic evaluation of the placenta and uterine artery Doppler between 18 and 22 weeks. Thrombophilia screen-negative women with two or three abnormal test categories were randomized by 23+6 weeks to self-administration of subcutaneous unfractionated heparin (UFH) 7500 IU twice daily until birth or 34 weeks, or to standard care. Maternal anxiety and other maternal-infant outcomes were determined. Thirty-two out of 41 eligible women consented, with 16 women randomized to UFH and 16 to standard care. There was no statistically significant difference identified between the two treatment groups (standard care vs. UFH) for the following: maternal anxiety score (mean [standard deviation]), 14.2 [± 1.6] vs. 14.0 [± 1.8]; birth weight (median [range]), 1795 [470-3295]g vs. 1860 [730-3050]g; perinatal death, 3 vs. 0; severe preeclampsia, 2 vs. 6; placental weight < 10th percentile, 7 vs. 4; or placental infarction, 4 vs. 3. Our study design identified women at high risk of adverse maternal-infant outcomes attributable to placental insufficiency. Women with evidence of placental insufficiency were willing to undergo randomization and self-administration of UFH without increased maternal anxiety.

Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones

BackgroundIn early pregnancy, increased plasma levels of the endocannabinoid anandamide (AEA) are associated with miscarriage through mechanisms that might affect the developing placenta or maternal decidua.MethodsIn this study, we compare AEA levels in failed and viable pregnancies with the levels of the trophoblastic hormones (beta-human chorionic gonadotrophin (beta-hCG), progesterone (P4) and (pregnancy-associated placental protein-A (PAPP-A)) essential for early pregnancy success and relate that to the expression of the cannabinoid receptors and enzymes that modulate AEA levels.ResultsThe median plasma AEA level in non-viable pregnancies (1.48 nM; n = 20) was higher than in viable pregnancies (1.21 nM; n = 25; P = 0.013), as were progesterone and beta-hCG levels (41.0 vs 51.5 ng/mL; P = 0.052 for P4 and 28,650 vs 6,560 mIU/L; P = 0.144 for beta-hCG, respectively, but were not statistically significant). Serum PAPP-A levels in the viable group were approximately 6.8 times lower than those in the non-viable group (1.82 vs 12.25 mg/L; P = 0.071), but again these differences were statistically insignificant. In the spontaneous miscarriage group, significant correlations between P4 and beta-hCG, P4 and PAPP-A and AEA and PAPP-A levels were observed. Simultaneously, immunohistochemical distributions of the two main cannabinoid receptors and the AEA-modifying enzymes, fatty acid amide hydrolase (FAAH) and N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), changed within both the decidua and trophoblast.ConclusionsThe association of higher AEA levels with early pregnancy failure and with beta-hCG and PAPP-A, but not with progesterone concentrations suggest that plasma AEA levels and pregnancy failure are linked via a mechanism that may involve trophoblastic beta-hCG, and PAPP-A, but not, progesterone production. Although the trophoblast, decidua and embryo contain receptors for AEA, the main AEA target in early pregnancy failure remains unknown.

The association between preeclampsia and placental disruption induced by chorionic villous sampling

The objectives of this study were (1) to evaluate if the elevation of maternal serum alpha-feto protein (MSAFP) and pregnancy-associated placental protein-A (PAPP-A) in the maternal blood after chorionic villous sampling (CVS) is associated with a higher preeclampsia (PE) rate and (2) to verify the clinical utility of the analytes elevation for predicting PE. A prospective study on 106 subjects who underwent CVS was performed. At the time of CVS, two blood samples were obtained for MSAFP and PAPP-A dosage, the first just before the procedure, and the second one 30 min after the procedure. Cases with abnormal karyotype, major anomalies or preterm delivery were subsequently excluded. The ratio between the two samples was calculated as Sigma (MSAFP or PAPP-A post-CVS/MSAFP or PAPP-A pre-CVS) and it was related to subsequent occurrence of PE. The rate of PE was 5.7% (6/106). Both MSAFP and PAPP-A levels were higher after than before CVS (median ratio = 8.33 and 1.08, respectively). Cases developing PE had significantly higher MSAFP ratio (11.6 vs 7.4, p-value = 0.04) and PAPP-A ratio (1.13 vs 1.08, p-value = 0.009) than those who did not develop PE. Receiver operating characteristic curve analysis showed that PAPP-A ratio was a better predictor of subsequent PE than MSAFP ratio: at a fixed false positive rate of 10%, the detection rates for MSAFP and PAPP-A ratios were 33 and 50%, respectively. The elevation of MSAFP and PAPP-A observed with CVS is associated with increased risk of subsequent PE. The ability of such increases to predict PE appears to be modest.

Screening for Placental Insufficiency in High-risk Pregnancies: Is Earlier Better?

Objective To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. Study design Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11–13 +6 weeks and at 18–23 +6 weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery < 32 weeks, or stillbirth). Results Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses < 20 weeks, 2 (3.3%) stillbirths > 20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries < 32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3–8.5; −LR: 0.63, 95% CI: 0.36–0.93; p = 0.025], as was ≥1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6–24; −LR: 0.68, 95% CI: 0.59–0.89; p = 0.005] or ≥2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3–7.7; −LR: 0.58, 95% CI: 0.27–0.94; p = 0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency ( p = 0.05, power 80%, z-test). Conclusions In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.

Novel Markers for the Evaluation of Patients With Suspected Ischemic Heart Disease

At present, for the evaluation of patients with suspected acute coronary syndromes (ACS), currently available cardiac biomarkers depend on the presence of myocyte necrosis or left ventricular dysfunction in order to be diagnostic. With a better understanding of the pathophysiology that underlies the ACS has come a wide variety of candidate cardiac biomarkers, whose ability to detect the pathophysiologic processes involved in ACS may represent a step forward for the practicing clinician. Included among these novel biomarkers are markers of myocardial ischemia in the absence of necrosis (ischemia modified albumin and free fatty acids), markers of plaque inflammation and/or instability (myeloperoxidase, pregnancy-associated placental protein-A, whole blood choline, lipoprotein-associated phospholipase A2), as well as markers of platelet activity (soluble CD40 ligand). The potential role of these novel markers in the evaluation of patients with suspected ACS will be reviewed.

Expression of Pregnancy-associated Plasma Protein-A (PAPP-A) During Human Villous Trophoblast Differentiation In Vitro

Pregnancy-associated placental protein-A (PAPP-A), first isolated from maternal serum, has been identified as a metalloprotease cleaving insulin-like growth factor binding protein-4 (IGFBP-4). The source of PAPP-A during pregnancy is unclear. We therefore investigated PAPP-A expression during in vitro human villous cytotrophoblast cell (CT) differentiation into syncytiotrophoblast (ST). CT were isolated from normal first trimester, second trimester and term placentae (n=10) and cultured to form ST. PAPP-A mRNA was quantified by real-time PCR, and PAPP-A protein expression was studied by immunocytochemistry and TRACE technology with specific monoclonal antibodies. PAPP-A mRNA expression in total placental extracts increased during the course of pregnancy. PAPP-A protein was detected in the cytoplasm of both CT and ST. ST formation in vitro was associated with a 19-fold increase in PAPP-A mRNA expression and an 8-fold increase in PAPP-A secretion into the culture medium. No significant difference in PAPP-A production was observed between cultured cells isolated from early and term placentae.In conclusion, PAPP-A production in vitro, is associated to the differentiation of villous cytotrophoblast cells into syncytiotrophoblast, independantly of the age of gestation.

Maternal serum concentrations of pregnancy associated placental protein A and pregnancy specific -1-glycoprotein in multifetal pregnancies before and after fetal reduction

Placental function in multifetal pregnancies before and after embryo reduction was investigated by measuring maternal serum concentrations of pregnancy associated placental protein-A (PAPP-A) and pregnancy specific beta-1-glycoprotein (SP-1). Three groups of pregnant women were studied following assisted reproduction; groups 1 and 2, were 12 singleton and 12 twin pregnancies respectively, and group 3 comprised 12 women with multifetal pregnancies undergoing embryo reduction. PAPP-A and SP-1 were measured serially at 8-21 weeks gestation. In all pregnancies, maternal serum PAPP-A and SP-1 increased with gestation. In twin pregnancies the mean concentrations of SP-1 were significantly higher than in singletons at all gestations, whereas for PAPP-A, concentrations were similar between these groups. In multifetal pregnancies before embryo reduction, the serum concentrations of both proteins were significantly higher than in twin pregnancies. Following reduction, the concentrations of PAPP-A remained significantly higher than for twins throughout, whereas the concentrations of SP-1 gradually converged towards those of twins; by 19 weeks there was no difference between the means of the two groups. These findings suggest that circulating concentrations of SP-1 reflect total placental mass, which is proportional to the number of live fetuses, whereas the pattern of PAPP-A changes suggests that this protein is produced by the placenta, decidua and other tissues.

First trimester serum screening for Down's syndrome.

Screening for Down's Syndrome has been shown to be effective at 10 weeks of pregnancy. A multicentre study (the first trimester serum screening study) has shown that there are two biochemical markers of choice at this time in pregnancy, namely pregnancy associated placental protein A (PAPP-A) and the free beta-sub-unit of human chorionic gonadotrophin (free beta-hCG). When used together with maternal age these two biochemical markers have an estimated detection rate of 62% and a 5% false-positive rate. The results are consistent with those obtained from a systematic review of the world literature. Other markers are less predictive of Down's syndrome though there is still some uncertainty over the value of dimeric inhibin-A at 10 weeks of pregnancy. Nuchal translucency measurement, from an ultrasound examination performed at about 10 weeks of pregnancy, is associated with Down's syndrome and is emerging as an important potential screening marker. At present there is uncertainty over its quantitative performance and performance when combined with biochemical markers. The resolution of these issues is currently the subject of active research. Ten week screening for Down's syndrome is an advance that is now technically possible though there is still insufficient information to justify its use in routine screening practice.

The relationship of uterine and umbilical Doppler resistance to fetal and placental protein synthesis in the second trimester

The relation of uteroplacental and umbilical Doppler resistance index (RI) to peripheral levels of alphafetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (HPL), Schwangerswaft protein (SP1), pregnancy-associated placental protein A (PAPP-A) and insulin-like growth factor binding protein 1 (IGP-BP1) at 16-24 weeks was established in a cross-sectional study of 183 unselected singleton pregnancies. There was an association between high values of uteroplacental RI and high hCG levels, and high umbilical RI values with high hCG and HPL levels. Thus, in the mid-trimester, the levels of some placental proteins seem to be related to placental resistance.

Evaluation of risk factors for the development of nonmalignant diseases of the cervix

The relation of uteroplacental and umbilical Doppler resistance index (RI) to peripheral levels of alphafetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (HPL), Schwangerswaft protein (SP1), pregnancy-associated placental protein A (PAPP-A) and insulin-like growth factor binding protein 1 (IGP-BP1) at 16–24 weeks was established in a cross-sectional study of 183 unselected singleton pregnancies. There was an association between high values of uteroplacental RI and high hCG levels, and high umbilical RI values with high hCG and HPL levels. Thus, in the mid-trimester, the levels of some placental proteins seem to be related to placental resistance.

Immunohistochemical localization of pregnancy-associated plasma protein a in decidua and trophoblast: Comparison with human chorionic gonadotrophin and fibrin

In an immunoperoxidase study, pregnancy-associated placental protein A (PAPP-A) was localized to the cytoplasm of decidual stromal cells, the villous syncytiotrophoblast and on the surface of placental trophoblast. A decidual and a trophoblastic origin is suggested for PAPP-A, and its presence on the surface of the syncytiotrophoblast is interpreted as a possible immunoprotective layer.