Comparison of the diagnostic accuracy of early screening for Preeclampsia by NICE guidelines, ACOG guidelines and comprehensive first trimester screening using maternal characteristics, ultrasonographic findings and maternal serum biochemical markers in the prediction of the development of Preeclampsia in a tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Introduction@#Preeclampsia remains to be a major cause of both fetal and maternal morbidity and mortality, particularly in severe forms leading to preterm birth. There is a lack of consensus, however, on the preferred screening test for early diagnosis with the aim of reducing the prevalence and morbidity of the disease. @*Objective@#To compare the performance of the comprehensive first trimester screening using maternal characteristics, ultrasonographic findings and serum biochemical markers, with the NICE and ACOG guidelines in predicting the development of preeclampsia. The study also aims to determine the compliance rate of clinicians in giving aspirin prophylaxis using the different screening tests. Methodology: This is a retrospective, analytical, cross sectional study of all pregnant patients between 11 to 13 6/7 weeks referred for comprehensive first trimester screening for preeclampsia from January 2014 to January 2018. Maternal factors were assessed to determine the risk of preeclampsia using NICE guidelines, ACOG guidelines and comprehensive first trimester screening. The compliance on aspirin administration for high-risk patients was also determined. The outcome measure was diagnosis of preeclampsia and the detection rate (DR) of the three screening tests were compared. @*Results@#A total of 202 women were included in the analysis where 24 (11.9%), 11 (5.4%) and 13 (6.4%) developed preeclampsia, early-onset preeclampsia (EO-PE) and late-onset preeclampsia (LO-PE) respectively. The NICE and ACOG guidelines were able to detect preeclampsia with an accuracy of 76.73% (Sn 75%, Sp 77% PPV 30.5%) and 43.07% (Sn 83.3%, Sp 37.6% PPV 15.3%) respectively. The comprehensive first trimester screening was able to detect preeclampsia with an accuracy of 89.60% (Sn 83.3%, Sp 90.5% PPV 54.1%). EO-PE and LO-PE were detected with an accuracy of up to 97.2% using the comprehensive screening (Sn 90.9%, Sp 97.9% PPV 71.4%), compared with the NICE guideline (up to 74.26%, Sn 81.8%, Sp 73.8% PPV 15.3%) and the ACOG guideline (up to 39.6%, Sn 90.9%, Sp 36.6, PPV 7.63%). Compliance with the NICE and ACOG recommendation on aspirin administration was only 42.37% and 33.33%, respectively, and this increased to up to 62% when comprehensive first trimester screening was used. @*Conclusion@#This study confirmed that the performance of screening for PE, and therefore appropriate selection of the patients that would benefit from prophylactic use of aspirin and closer surveillance, is by far superior if the comprehensive first trimester screening is used than the method advocated by ACOG and NICE.

Marcadores séricos del primer trimestre y riesgo obstétrico en una población con alta prevalencia de obesidad / First-trimester serum markers and obstetric risk in a population with a high prevalence of obesity

Objetivo: La detección precoz del riesgo de complicaciones de la gestación como preeclampsia, parto pretérmino, y aborto, permitiría evitar morbimortalidad y secuelas. Hemos estudiado la relación entre niveles bajos de PAPP-A y BhCG con malos resultados obstétricos en una población con alta prevalencia de obesidad. Material y métodos: Estudio retrospectivo de casos y controles anidado en una cohorte de pacientes que acudieron para tamizaje de aneuploidías el I trimestre. Los casos fueron las pacientes con MoM PAPPA y/o BhCG por debajo del percentil 5 y el grupo control una muestra aleatorizada de pacientes con marcadores normales. Se ajustó por obesidad, edad, paridad, tabaquismo, y técnicas de reproducción. Resultados: La cohorte estuvo formada por 9111 pacientes. Se obtuvieron 382 casos con MoM PAPP-A inferior al percentil 5 y 325 con MoM BhCG por debajo del percentil 5, y 50 casos con ambos marcadores por debajo del percentil 5. Se tomaron 1417 controles. La prevalencia de obesidad fue del 20,7% y de sobrepeso el 28,4%. Los niveles bajos de PAPP-A se relacionaron con abortos, preeclampsia, crecimiento intrauterino retardado, pequeños para la edad gestacional, parto pretérmino y diabetes gestacional. Los niveles de BhCG por debajo del percentil 5 se relacionaron con la enfermedad hipertensiva gestacional. Los niveles de ambos marcadores por debajo del percentil 5 tuvieron relación significativa con aborto, preeclampsia precoz y parto pretérmino. Conclusión: Los niveles bajos de PAPP-A y BhCG se relacionan con malos resultados obstétricos en una población de alta prevalencia de obesidad.

Background: Early identification of pregnant women at risk of developing intrauterine growth restriction, preeclampsia, preterm birth, stillbirth, among other complications would allow more intensive surveillance to reduce the risk of severe disease. We aimed to study whether low levels of maternal serum markers PAPP-A and BHCG are associated with adverse pregnancy outcomes in an obese population. Methods: Cases were obtained from a cohort of 9111 patients who attended first trimester screening. We included women with PAPP-A and/or BHCG below the 5th percentile. A randomized group of women with serum markers above the 5th percentile was used as control group. Results were adjusted for age, parity, smoking status, BMI or reproductive techniques. Results: Prevalence of obesity was 20,7%. We found 382 women with PAPP-A below the 5th percentile, 325 with BHCG below the 5th percentile, 50 with both markers low, and recruited 1417 controls. The cases with low PAPP-A were significantly more likely to experience abortion, preeclampsia, low birth weight, preterm birth, or gestational diabetes. Low BHCG was significantly associated with gestational hypertension. Low BHCG and PAPP-A in the same patient correlated with abortion, early preeclampsia and preterm birth. Conclusions: Low levels of maternal serum markers correlate with adverse pregnancy outcomes in an obese population. We recommend to develop further calculators of obstetric risk to improve positive predictive value and to establish a maternal-fetal surveillance plan.

Maternal serum placental growth factor and pregnancy-associated plasma protein A measured in the first trimester as parameters of subsequent pre-eclampsia and small-for-gestational-age infants: A prospective observational study

OBJECTIVE: To examine the first-trimester maternal serum placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) levels in pregnancies associated with pre-eclampsia (PE) or small-for-gestational-age (SGA) infants, and determine the predictive accuracy of PlGF and of PAPP-A for either PE or SGA infants. METHODS: This prospective, observational study included 175 pregnant women, and of these women, due to participant withdrawal or loss to follow-up, delivery data were collected from the medical records of 155 women, including 4 who had twin pregnancies. The women's maternal history was recorded, and the PlGF and PAPP-A levels at 11 to 13 gestational weeks were measured. During the second trimester, the maternal uterine artery's systolic/diastolic ratio was measured. Multiples of the median (MoM) of PlGF and PAPP-A were determined, and the associations of these values with the risk factors of SGA and PE were evaluated. Logistic regression analysis was used to determine whether PlGF and PAPP-A are useful markers for predicting SGA infants. RESULTS: The PAPP-A MoM level was significantly lower in women with advanced maternal age, multipara women, and women with gestational diabetes than in their counterparts. The PlGF and PAPP-A MoM levels were higher in women with a twin pregnancy than in those with a singleton pregnancy. There was a significant relationship between the maternal serum PAPP-A MoM level in the first trimester and the uterine artery systolic/diastolic ratio in the second trimester. Results of logistic regression analysis showed that low PlGF and PAPP-A MoM levels were predictors of SGA infants (odds ratio, 0.143; 95% confidence interval, 0.025 to 0.806; odds ratio, 0.191; 95% confidence interval, 0.051 to 0.718, respectively). CONCLUSION: PlGF and PAPP-A are potentially useful as first-trimester markers for SGA infants and some hypertensive disorders of pregnancy.

Asociación de nivel bajo de PAPP-A en primer trimestre con resultados obstétricos adversos / Association of low PAPP-A level in the first trimester with adverse obstetric outcomes

ANTECEDENTES: La PAPP-A es una proteína utilizada en obstetricia de forma rutinaria para el cribado de aneuploidías de primer trimestre. En los últimos años se está conociendo más acerca de su papel en la función placentaria. Diversos estudios están mostrando una asociación entre un nivel bajo de PAPP-A y distintos eventos obstétricos. OBJETIVO: Establecer una asociación entre PAPP-A baja y eventos obstétricos adversos. MÉTODO: Estudio retrospectivo de casos y controles anidado en una cohorte. Se han recogido las gestaciones únicas con PAPP-A inferior a percentil 5 en primer trimestre durante 2 años. Se ha recogido de la misma cohorte un grupo control, en proporción 2:1. Se compara mediante análisis estadístico la incidencia de eventos obstétricos adversos de cada grupo. RESULTADOS: Se incluyó un total de 285 pacientes en el grupo de casos y 570 pacientes en el grupo control. Se observó un aumento significativo en el grupo de casos de la incidencia de prematuridad, restricción del crecimiento, hipertensión gestacional y diabetes gestacional. Se ha correlacionado la PAPP-A baja con varios eventos obstétricos adversos, incluyendo prematuridad (OR 4,27), diabetes gestacional (OR 2,40), restricción del crecimiento (OR 2,36) e hipertensión gestacional (OR 2,22). No se observó relación con el resto de eventos obstétricos adversos. CONCLUSIÓN: Un nivel de PAPP-A bajo se asocia con aumentos significativos de prematuridad, diabetes gestacional, restricción del crecimiento e hipertensión gestacional.

BACKGROUND: PAPP-A is a placental protein used in obstetrics as a first trimester marker in aneuploidy screening. In the last few years we are knowing more about its placental function. Some studies are showing a association between low PAPP-A and obstetrical adverse events. AIM: Establish an association between low PAPP-A an obstetrical adverse events. METHOD: This is a retrospective nested case-control study. We identified each singleton pregnancy with a normal phenotype and a low PAPP-A (under percentile 5) in the last 2 years, and match it with a control group of the same population in a 2:1 proportion. It was compared the incidence of each obstetrical adverse outcomes with statistical analysis. RESULTS: We found 285 patients in the case group and match it with 570 patients from control group. It was observed a significative increase in the incidence of prematurity, intrauterine growth restriction, gestational hypertension and gestational diabetes. A low PAPP-A level was correlated with some obstetrical adverse events, like prematurity (OR 4.27), gestational diabetes (OR 2.40), intrauterine growth restriction (OR 2.36) and gestational hypertension (OR 2.22). We observe no correlation with the rest of outcomes. CONCLUSIONS: A low PAPP-A level is related with significative increases of prematurity, gestational diabetes, intrauterine growth restriction and gestational hypertension.

Asociación entre el sistema IGF y PAPP-A en ateroesclerosis coronaria / Association between IGF system and PAPP-A in coronary atherosclerosis

Resumen La aterosclerosis es una enfermedad que involucra múltiples mecanismos fisiopatológicos cuyo conocimiento no se ha dilucidado por completo. Con frecuencia, los avances científicos sobre la fisiopatología aterogénica generan que a diversas moléculas no consideradas previamente en el panorama de dicha enfermedad se les atribuyan acciones sobre el inicio o progresión de la misma. Un ejemplo representativo es el estudio de un nuevo mecanismo involucrado en el proceso aterogénico, consistente en la asociación entre el sistema de factores de crecimiento similares a la insulina (IGF) y la proteína plasmática A asociada al embarazo (PAPP-A). El sistema IGF es una familia de péptidos compuesto por 3 hormonas peptídicas, 4 receptores transmembranales y 6 proteínas transportadoras. El factor de crecimiento similar a la insulina tipo 1 (IGF-1) es el principal ligando del sistema IGF involucrado en la aterosclerosis coronaria y ejerce sus efectos mediante la activación del receptor IGF-1R en células de músculo liso vascular de las arterias coronarias o en macrófagos de placas ateroscleróticas. En células de músculo liso vascular promueve la migración y previene la apoptosis aumentando la estabilidad de la placa, y en macrófagos disminuye el transporte reverso de colesterol propiciando la formación de células espumosas. La regulación de la biodisponibilidad de IGF-1 en el endotelio se lleva a cabo por las proteasas de proteínas IGFBP, principalmente por la PAPP-A. En la presente revisión se abordan los mecanismos involucrados entre el sistema IGF y la PAPP-A en aterosclerosis coronaria con énfasis en los efectos moleculares producidos en células de músculo liso vascular y en macrófagos.

Abstract Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages.

Screening for chromosomal abnormalities using combined test in the first trimester of pregnancy

OBJECTIVE: This study was designed to review the screening performance of combined test at the Ewha Womans University Mokdong hospital. METHODS: All women admitted for routine antenatal care between January 1st 2008 and December 31st 2012 with a known pregnancy outcome were included in this study, totaling 1,156 women with singleton pregnancies presenting at 10 to 13 weeks of gestation. Women were offered screening using a combination of maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin and fetal nuchal translucency thickness. Those with an estimated risk of ≥1 in 250 of carrying a fetus with trisomy 21 or ≥1 in 300 risk of trisomy 18 were offered genetic counseling with the option of an invasive diagnostic test. RESULTS: The median of gestational age was 11+3 weeks, the median of crown-rump length was 47.1 mm, and the median age of the women was 31 years. The detection rate was 80% for trisomy 21 (4 of 5) and 100% for trisomy 13 and 18 (all 2). The false-positive rate was 7.73% for trisomy 21 and 1.21% for trisomy 18. CONCLUSION: This study was the first large population study performed with the aim of analyzing the performance of the combined test in Korea. This study demonstrated that the detection rates and other figures of the first trimester combined test are comparable to the results reported in other papers worldwide. Consequently, if strict conditions for good screening outcomes are achieved, the first trimester combined test might well be the earliest detectable screening, improving detection rates without increasing karyotyping or economic and other implications that inevitably ensue.

Screening for chromosomal abnormalities using combined test in the first trimester of pregnancy

OBJECTIVE: This study was designed to review the screening performance of combined test at the Ewha Womans University Mokdong hospital. METHODS: All women admitted for routine antenatal care between January 1st 2008 and December 31st 2012 with a known pregnancy outcome were included in this study, totaling 1,156 women with singleton pregnancies presenting at 10 to 13 weeks of gestation. Women were offered screening using a combination of maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin and fetal nuchal translucency thickness. Those with an estimated risk of ≥1 in 250 of carrying a fetus with trisomy 21 or ≥1 in 300 risk of trisomy 18 were offered genetic counseling with the option of an invasive diagnostic test. RESULTS: The median of gestational age was 11+3 weeks, the median of crown-rump length was 47.1 mm, and the median age of the women was 31 years. The detection rate was 80% for trisomy 21 (4 of 5) and 100% for trisomy 13 and 18 (all 2). The false-positive rate was 7.73% for trisomy 21 and 1.21% for trisomy 18. CONCLUSION: This study was the first large population study performed with the aim of analyzing the performance of the combined test in Korea. This study demonstrated that the detection rates and other figures of the first trimester combined test are comparable to the results reported in other papers worldwide. Consequently, if strict conditions for good screening outcomes are achieved, the first trimester combined test might well be the earliest detectable screening, improving detection rates without increasing karyotyping or economic and other implications that inevitably ensue.

Proteína plasmática A asociada al embarazo y fracción β de gonadotrofina coriónica humana en pacientes con resultados materno y perinatal adverso: informe preliminar / Plasma protein associated with pregnancy and β fraction human chorionic gonadotropin results in patients with adverse maternal and perinatal: preliminary report

Objetivo: Evaluar el comportamiento de marcadores bioquímicos: proteína plasmática asociada al embarazo (PAPP-A) y fracción β de la hormona gonadotrofina coriónica (β hCG) con resultado materno y perinatal adverso en el Hospital “Dr. Adolfo Prince Lara”. Métodos: Estudio prospectivo, comparativo en 35 gestantes con embarazos simples entre las 11 y 13 semanas + 6 días y resultado del embarazo conocido. Se realizó tamizaje combinado: traslucencia nucal, hueso nasal, ductus venoso, longitud craneocaudal y marcadores bioquímicos (PAPP-A y β -hCG). Se determinó la concentración de PAPP-A y β -hCG y sus resultados se expresaron en MoM. Variables cuantitativas fueron expresadas en media y desviación estándar (DE), cualitativas en porcentajes y se compararon estas variables entre el grupo de gestantes con resultado materno perinatal normal (RMPN) y adverso (RMPA) con la prueba U de Mann-Whitney. Resultados: 71 % tuvieron un RMPN y 29 % RMPA. No se encontraron diferencias entre los grupos respecto a edad materna, peso materno, IMC, paridad, presión arterial. La PAPP-A expresado en MoM presentan un valor más alto en las embarazadas que tuvieron un RMPA (1,07 vs 1,43) siendo estadísticamente significativo, los valores de β-HCG tuvieron valores más altos (0,60 vs 0,76) entre el grupo con RMPA en relación al grupo con RMPN sin llegar a la significancia estadística. Conclusión: Valores de la MoM PAPP-A difieren en las embarazadas con RMPA de aquellas con resultado normal, pero con valores mayores en las primeras, contrario a lo encontrado en la mayoría de las publicaciones estudiadas, iguales hallazgos con la β-hCG. Se debe profundizar en estos estudios para verificar los resultados encontrados.

Objective: To evaluate the behavior of biochemical markers PAPP-A and β hCG with adverse pregnancy and perinatal outcomes. Methods: Prospective, comparative study in 35 pregnant women with singleton pregnancies between 11 and 13 weeks + 6 days and outcome of pregnancy known. Nuchal translucency, nasal bone, ductus venosus, rump length and biochemical markers (PAPP-A and β-hCG) combined screening was performed. The concentration of PAPP-A and β-hCG was determined and the results were expressed in MoM. Quantitative variables were expressed as mean and standard deviation (SD), and these percentages qualitative variables between the group of pregnant women with a normal perinatal maternal outcome (NPMO) and adverse (AMPO) with the U Mann-Whitney test were compared. Setting: Hospital “Dr. Adolfo Prince Lara”. Results: 71 % had a NPMO and 29 % had an AMPO. No differences between the groups in respect of maternal age, maternal weight, BMI, parity, blood pressure were found. PAPP-A MoM have expressed a higher value in pregnant having an AMPO (1.07 vs 1.43) were statistically significant, the values of β-HCG had higher values (0.60 vs 0.76) between the group with AMPO relative to NMPO group without reaching statistical significance. Conclusion: MoM values of PAPP-A differ in pregnant with AMPO than in those with normal results, but with higher values in the first opposite to that found in most of the studied publications, the same findings with β-hCG. Thus, it should look into these studies to verify the results found.

Results of prenatal screening for fetal chromosome abnormality during the first trimester pregnancy in Guangzhou / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the efficiency of first trimester prenatal screening for fetal chromosome abnormality using maternal serum marker test and(or) plus nuchal translucency (NT) in Guangzhou region.</p><p><b>METHODS</b>The results of prenatal screening were retrospectively analyzed among 43 703 women with singleton pregnancies from January 2007 to September 2012. A total of 43 703 pregnancies between 9 and 13(+6) weeks of pregnancy were collected and analyzed for maternal serum pregnancy-associated plasma protein A (PAPPA), free β -human chorionic gonadotropin (free β -hCG) with or without crown-rump length (CRL). Nuchal translucency was measured by ultrasonographic scan between 11 and 13(+6) weeks of pregnancy. Gestational age was estimated by ultrasonographic scan. The risk values of Down syndrome (DS) and trisomy 18 were calculated using the software Lifcycle. Comparing the difference between the combined screening (PAPPA, free β -hCG and NT) and serum marker screening (PAPPA and free β -hCG).</p><p><b>RESULTS</b>Among the 43 703 pregnant women, screening showed that 1385 (3.17%) were Down syndrome positive and 55 (0.13%) were trisomy 18 positive. The final outcomes of pregnancy showed that 142 cases presented chromosomal abnormalities, of which 54 cases suffered from Down syndrome, 13 had trisomy 18, and 75 had other chromosome abnormalities. The total detection rate of Down syndrome and trisomy 18 were 83.33% and 76.92%, respectively.The positive rate is lower, and the detection rate is higher in combined screening group than serum marker screening group. The median PAPPA MoM was lower and the median free β -hCG MoM and NT measured value was higher in Down syndrome pregnancies than control group. The median PAPPA and free β -hCG MoM were lower and the median NT measured value was higher in trisomy 18 pregnancies than control group.</p><p><b>CONCLUSION</b>The first trimester prenatal screening can effectively detect Down syndrome and trisomy 18 pregnancy. The combined screening method is superior to the serum marker screening and is the preferred strategy in the first trimester prenatal screening.</p>

[ relationship between CRL and PAPP-A measurements in first trimester fetuses with low birth weight]

Recent studies have suggested that impaired fetal growth are indicators that may be present in the first trimester. The aim of this study was to investigate the relationship between crown-rump length [CRL] and pregnancy associated plasma protein-A [PAPP-A] measurements in first trimester for low birth weight [LBW]. This prospective cohort study were on 120 pregnant women in first pregnancy trimester, in Women's Hospital Mirza Kochak Khan in 2011-2012. Gestational age according to crown-rump length and gestational age according to last menstrual period [LMP], neonatal weight, small for gestational age, pregnancy associated plasma protein-A and low birth weight were recorded. Main outcome measures was weight and gestational age at birth. Statistical tests used included descriptive statistics, t-test, X[2] and all tests were two-tailed and differences with P<0.05 were considered to be statistically significant. Our findings showed that a total of 120 cases were included CRL Z-score and log 10 [MOM PAPP-A] were positively correlated with fetal birth weight. The mean Crown-rump length Z-score was significantly can be reduced in LBW in first trimester pregnancy. [P<0.001] Mean PAPP-A in low birth weight was [0.4 +/- 0.11 MOM], but in normal weight infants was [1.04 +/- 0.7 MOM]. [P=0.011] also mean PAPP-A in pregnant women with SGA infants is significantly less than other pregnant women [0.5 +/- 0.2 versus 1.1 +/- 0.7] [P<0.001]. Our data suggest that crown-rump length and maternal levels of PAPP-A measured during the first trimester are independent factors that influence fetal birth weight. But their predictive powers are not sufficiently good for them to be used alone for low birth weight screening.

Prognostic value of ultra-sensitive pregnancy associated plasma protein-A in patients with acute coronary syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the prognostic value of ultra-sensitive pregnancy associated plasma protein-A (PAPP-A) level in the early phase of acute coronary syndrome (ACS) attack.</p><p><b>METHODS</b>Patients diagnosed as ACS were enrolled and the level of circulatory PAPP-A was measured within 12 hours after ACS attack. The patients were followed at the time of 1st, 6th, and 12th months post-ACS attack in order to observe the incidence of the cardiovascular adverse events. According to the highest quintile, the patients were divided into 2 groups: high level (≥26.08 μg/L) group and low level (<26.08 μg/L) group, to evaluate the association between the level of PAPP-A and the incidence of the cardiovascular events.</p><p><b>RESULTS</b>Compared with the low level group, the incidence of the composite outcome is significantly increased in the high level group, and the values of OR are 4.76, 4.38, 3.75 for 1st, 6th, 12th months respectively (P=0.000). For myocardial infarction (MI) + cardiac death (CD) the values of OR were 9.81, 6.08, 4.12 (P<0.01). Multivariate logistic regression analysis demonstrates that PAPP-A was an independent risk factor for the cardiovascular adverse events in the early, median, and late phase of ACS (P<0.05).</p><p><b>CONCLUSION</b>In the early phase of ACS attack, the elevation of PAPP-A is an independent risk factor for the occurrence of cardiovascular adverse events.</p>

Research on the relationship between levels of soluble cluster of differentiation 40 ligand, matrix metalloproteinase 9 and pregnancy-associated plasma protein A in serum and stability of carotid plaques / 中华外科杂志

<p><b>OBJECTIVES</b>To study the relationship between serum levels of some inflammatory markers and stability of carotid plaques in the patients with carotid plaques and evaluate the ability of each serum marker in identifying vulnerable carotid plaques.</p><p><b>METHODS</b>The study included 65 consecutive patients with carotid plaques confirmed by imaging examinations from March 2008 to March 2010. All the patients were classified as stable plaques group (n = 21) and unstable plaques group (n = 44) according to the characteristic findings of the plaques in MRI such as the thickness of fibrous cap, the existence of large lipid core and the intra-plaque hemorrhage. The patients of unstable plaques group were further classified as unruptured plaques group (n = 29) and rupture plaques group (n = 15) according to the integrity of fibrous cap. Serum levels of soluble cluster of differentiation 40 ligand (sCD40L), matrix metalloproteinase 9 (MMP-9) and pregnancy-associated plasma protein A (PAPP-A) were determined by ELISA.</p><p><b>RESULTS</b>Serum levels of sCD40L and MMP-9 in patients of unstable plaques group, unruptured plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group (SCD40L: χ(2) = 6.45, 12.04 and 16.23, P < 0.01; MMP-9; F = 2.55, 5.10 and 4.69, P < 0.05). Serum levels of PAPP-A in patients of unstable plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group (χ(2) = 11.71 and 13.55, P < 0.05). Serum levels of PAPP-A in patients of rupture plaques group were significantly enhanced compared to individuals of unruptured plaques group (χ(2) = 13.19, P = 0.000). sCD40L ≥ 673.22 ng/L (OR = 22.47, 95%CI: 2.11 - 239.81, P = 0.010), MMP-9 ≥ 84.09 µg/L (OR = 10.01, 95%CI: 1.74 - 57.78, P = 0.010) and PAPP-A ≥ 0.101 µg/L (OR = 14.29, 95%CI: 2.69 - 75.90, P = 0.002) were all significantly correlated with the vulnerability of carotid plaques.</p><p><b>CONCLUSIONS</b>There appear to be a relationship between the serum levels of sCD40L, MMP-9 and PAPP-A and the stability of carotid plaques in patients with carotid plaques. High serum levels of the above-mentioned markers may indicate that the plaques were vulnerable or ruptured.</p>

Análise do rastreamento combinado no primero trimestre da gestação para detecção de anomalias cromossômicas / Analysis of the combined first trimester screening for chromosomal abnormalities

OBJETIVO: avaliar o desempenho do rastreamento combinado do primeiro trimestre da gestação na detecção de anomalias cromossômicas em um grupo da população brasileira. MÉTODO: estudo retrospectivo envolvendo gestantes com feto único, referidas ao setor de medicina fetal para a realização do teste de rastreamento do primeiro trimestre da gestação pela combinação da idade materna, a medida da translucência nucal e dois marcadores bioquímicos do soro materno: free B-hCG e PAPP-A. Para avaliar o desempenho do teste foram calculados a sensibilidade, especificidade, valores preditivos positivos e negativos e as taxas de falso positivo, considerando como risco elevado valores superiores a 1:300. RESULTADOS: foram incluídas 456 gestantes submetidas ao teste. A idade materna avançada, acima de 35 anos, ocorreu em 36,2 por cento dos casos. A incidência de cromossomopatia na população estudada foi de 2,2 por cento. Vinte e uma das gestantes (4,6 por cento) apresentou risco elevado ao teste (superior a 1:300). Usando-se este ponto de corte, a sensibilidade do teste foi de 70 por cento para as cromossomopatias em geral e 83,3 por cento para os casos de trissomia do cromossomo 21, com taxa de falso positivo de 3,1 por cento. CONCLUSÃO: o rastreamento combinado do primeiro trimestre foi eficaz na detecção das anomalias cromossômicas, principalmente em relação aos casos de trissomia 21, com baixas taxas de falso positivo. Observou-se importante contribuição do teste em reduzir a indicação do exame invasivo comparado ao uso da idade materna como fator de risco.

PURPOSE: to evaluate the performance of the combined first trimester screening for chromosomal abnormalities in a group of the Brazilian population. METHODS: a retrospective study including pregnant women with single fetuses referred to a fetal medicine center to perform the first trimester screening that combines maternal age, nuchal translucency measurement and two maternal serum biochemical markers: free B-hCG and PAPP-A. To evaluate the performance of the test, the detection rate, specificity, negative and positive predicted values and false-positive rates were calculated, considering as high risk the cut-off value above 1 in 300. RESULTS: we studied 456 patients submitted to the test. Advanced maternal age above 35 years was observed in 36.2 percent of cases. The incidence of chromosomal abnormalities in the study population was 2.2 percent. Twenty-one patients (4.6 percent) presented a high risk (above 1:300) by the combined test. Using this cut-off level, the detection rate of the test was 70 percent for all chromosomal abnormalities and 83.3 percent for trisomy 21, for a false-positive rate of 3.1 percent. CONCLUSIONS: the combined first trimester screening was effective to detect chromosomal abnormalities, mainly for trisomy 21, with low false-positive rates. The combined test contributed to decreasing the indication of an invasive test if we compare to maternal age alone as a risk factor.

Evaluation of stable coronary artery disease by multiple cardiac biomarkers

Effective management of stable coronary artery disease [SCAD] relies on early detection of coronary atherosclerosis. The objective was to evaluate diagnostic accuracy and risk stratification of SCAD patients by high sensitivity C reactive protein [hs CRP], Myeloperoxidase [MPO] and Pregnancy Associated Plasma Protein-A [PAPP-A]. validation study was conducted at Pathology Department of the Army Medical College, in collaboration with Armed Forces Institute of Cardiology [AFIC/NIHD] Rawalpindi. Total 122 subjects consisting of 61 patients of SCAD and 61 angio-negative controls were included. The levels of biomarkers were measured before angiography by using kits provided by Siemens [UK] for hs CRP and Abbott for MPO on Immulite 1000 and Architect Analyzer respectively, whereas serum PAPP-A was measured by an ELISA based method using kit provided by IBL Germany. The mean age of the patients was 56.57 +/- 8.35 years and consisted of 53 [86.9%] males and 8 [13%] females. Area under curve [AUC] and 95% CI of hs CRP 0.817 [0.736-.881] was significantly higher than that of MPO 0.685 [0.594-0.766] [p=0.018] and PAPP-A 0.565 [0.472-0.655] [p<0.001] for the diagnosis of SCAD. Patients in the highest quartile of PAPP-A were at the highest risk for adverse events as PAPP-A had the highest Hazard Ratio [HR] of 3.4 [p=0.004], as compared to hs CRP 1.124 [p=0.191] and MPO 0.998 [p=0.176]. hs CRP has superior diagnostic ability for detection of SCAD than MPO whereas PAPP-A is a more reliable marker for risk stratification among the cardiac biomarkers

Evaluation on the relationship between pregnancy associated plasma protein-a and intravascular ultrasound detected culprit coronary plaque morphology in patients with unstable angina / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the relationship between pregnancy associated plasma protein-A (PAPP-A) and culprit coronary plaque morphology in patients with unstable angina (UA).</p><p><b>METHODS</b>Sixty-eight UA patients undergoing diagnostic coronary angiography and intravascular ultrasound were included in this study. A sandwich enzyme-linked immunosorbent assay technique was used to assay the circulating PAPP-A. Plaque characteristics of culprit lesion were analyzed for UA patients with various PAPP-A levels.</p><p><b>RESULTS</b>PAPP-A level was significantly higher in high-risk UA than in non-high-risk UA [(19.9 ± 20.1) mIU/L vs. (6.9 ± 5.7) mIU/L, P = 0.002]. Optimal threshold of PAPP-A to predict high-risk UA was determined as 11.0 mIU/L with a sensitivity of 78.6% and a specificity of 77.5%. Patients with higher PAPP-A level (≥ 11.0 mIU/L) was associated with larger external elastic membrane cross-sectional area, plaque area and more plaque burden compared with patients with lower PAPP-A level (all P < 0.01). Positive remodeling, attenuated plaque and plaque rupture were significantly more often in patients with higher PAPP-A than in patients with lower PAPP-A level (all P < 0.01). PAPP-A ≥ 11.0 mIU/L (OR = 5.921, P = 0.014) and attenuated plaque (OR = 7.541, P = 0.038) were independent risk predictors for high-risk UA.</p><p><b>CONCLUSIONS</b>PAPP-A was associated with instability of culprit plaque in UA patients. PAPP-A ≥ 11.0 mIU/L and attenuated plaque were independent predictors for high-risk UA.</p>

Diagnostic Performance of High-Sensitivity Troponin T, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A Assays for Triage of Patients with Acute Myocardial Infarction / 대한진단검사의학회지

BACKGROUND: Early diagnosis is the cornerstone of management of acute myocardial infarction (AMI). We aimed to compare the diagnostic accuracy of high-sensitivity troponin T (hs-cTnT) with myeloperoxidase (MPO) and pregnancy-associated plasma protein A (PAPP-A) for early diagnosis of AMI in patients at the time of presentation to the emergency department (ED). METHODS: We enrolled 289 patients who presented at the ED of the National Institute of Heart Disease (NIHD) Rawalpindi, Pakistan, within 4 hr of onset of chest pain. Clinical assessment, electrocardiography (ECG), and angiography were carried out. Blood samples were collected at 0, 3, 6, and 12 hr. Analyses of plasma hs-cTnT, MPO, and PAPP-A were carried out using commercial kits. RESULTS: Out of 289 subjects who presented to the ED, we diagnosed 180 patients with coronary heart disease as having AMI (N=61) and 119 as without AMI (stable coronary artery disease, N=61; unstable angina, N=58). Compared to non-AMI patients, the patients with AMI had significantly higher levels (represented here as median [inter quartile range]) of plasma hs-cTnT (136 [39-370] vs. 12 [7-21] ng/L), MPO (906 [564-1,631] vs. 786 [351-1,299] pmol/L) and PAPP-A (5.78 [2.67-13.4] vs. 2.8 [1.8-4.9] mIU/L). Receiver operator characteristic curves (95% CI) for hs-cTnT (0.952 [0.909-0.978]) were significantly higher (P<0.001) than those for MPO (0.886 [0.830-0.929]) and PAPP-A (0.797 [0.730-0.854]), with AMI sensitivity and specificity percentages of 87% and 98% (hs-cTnT), 82% and 84% (MPO), and 65% and 87% (PAPP-A), respectively. CONCLUSIONS: The diagnostic performance of hs-cTnT was superior to that of MPO and PAPP-A for early triage and diagnosis of AMI among patients of coronary heart disease presenting with chest pain to the ED.

Diagnostic Performance of High-Sensitivity Troponin T, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A Assays for Triage of Patients with Acute Myocardial Infarction / 대한진단검사의학회지

BACKGROUND: Early diagnosis is the cornerstone of management of acute myocardial infarction (AMI). We aimed to compare the diagnostic accuracy of high-sensitivity troponin T (hs-cTnT) with myeloperoxidase (MPO) and pregnancy-associated plasma protein A (PAPP-A) for early diagnosis of AMI in patients at the time of presentation to the emergency department (ED). METHODS: We enrolled 289 patients who presented at the ED of the National Institute of Heart Disease (NIHD) Rawalpindi, Pakistan, within 4 hr of onset of chest pain. Clinical assessment, electrocardiography (ECG), and angiography were carried out. Blood samples were collected at 0, 3, 6, and 12 hr. Analyses of plasma hs-cTnT, MPO, and PAPP-A were carried out using commercial kits. RESULTS: Out of 289 subjects who presented to the ED, we diagnosed 180 patients with coronary heart disease as having AMI (N=61) and 119 as without AMI (stable coronary artery disease, N=61; unstable angina, N=58). Compared to non-AMI patients, the patients with AMI had significantly higher levels (represented here as median [inter quartile range]) of plasma hs-cTnT (136 [39-370] vs. 12 [7-21] ng/L), MPO (906 [564-1,631] vs. 786 [351-1,299] pmol/L) and PAPP-A (5.78 [2.67-13.4] vs. 2.8 [1.8-4.9] mIU/L). Receiver operator characteristic curves (95% CI) for hs-cTnT (0.952 [0.909-0.978]) were significantly higher (P<0.001) than those for MPO (0.886 [0.830-0.929]) and PAPP-A (0.797 [0.730-0.854]), with AMI sensitivity and specificity percentages of 87% and 98% (hs-cTnT), 82% and 84% (MPO), and 65% and 87% (PAPP-A), respectively. CONCLUSIONS: The diagnostic performance of hs-cTnT was superior to that of MPO and PAPP-A for early triage and diagnosis of AMI among patients of coronary heart disease presenting with chest pain to the ED.

Effect of passive smoking on the levels of pregnancy associated plasma protein -a in normal rats

To measure the levels of pregnancy associated plasma protein- A [PAPPA-A] in normal rats exposed to cigarette smoke. Experimental interventional study. Army Medical College, Rawalpindi, in collaboration with national institute of health [NIH], Islamabad. Total duration was of 4 weeks. Sixty albino rats of Sprague- Dawley strain weighing 200-250 gm, divided into two groups. Both the groups were kept in identical chambers. One group of 30 rats was further exposed to passive cigarette smoke for 4 weeks. No increase was observed in the levels of serum PAPP-A of both the groups: Passive smokers and not exposed to passive smoking i.e. P > 0.05. Smoking does not increase the levels of PAPP-A