Predictive value of serum Lp-PLA2, PAPP-A combined with C-peptide in patients with gestational diabetes mellitus in predicting neonatal hypoglycemia / 中华内分泌外科杂志

Objective:To observe the predictive value of serum LP-PLA2, PAPP-A and C-peptide for patients with diabetes (GDM) patients during pregnancy.Methods:From Jan.2018 to Jan. 2022, 400 patients with gestational diabetes mellitus (GDM group) and 400 healthy pregnant women who underwent prenatal examinations (control group) were enrolled. The serum prenatal lipoprotein-associated phospholipase A2 (Lp-PLA2) , pregnancy-associated plasma protein-A (PAPP-A) , C-peptide and neonatal blood glucose levels were compared between the two groups. The correlation of serum Lp-PLA2, PAPP-A and C-peptide with neonatal hypoglycemia in GDM patients was analyzed, and the value of area under receiver operating curve (ROC) for predicting neonatal hypoglycemia was analyzed.Results:The serum levels of Lp-PLA2, PAPP-A and C-peptide in the GDM group were higher than those in the control group (33.57±6.52 nmol/min/ml vs 23.45±4.38 nmol/min/ml, 26.72±4.79 ng/ml vs 23.57±3.08 ng/ml, 27.32±3.97 ng/mL vs 25.15±0.71 ng/mL) ( P<0.05) . The incidence of neonatal hypoglycemia in the GDM group was higher than that in the control group (16.0% vs 4.5%) ( P<0.05) .The serum levels of Lp-PLA2, PAPP-A and C-peptide in GDM patients with neonatal hypoglycemia were higher than those in neonatal normoglycemic patients (35.82±6.42 nmol/min/ml vs 32.29±6.03 nmol/min/ml, 27.72±4.21 ng/ml vs 25.35±3.98 ng/ml, 32.39±4.78 ng/mL vs 22.18±3.94 ng/mL) ( P<0.05) . Logistic regression analysis showed that high levels of serum Lp-PLA2, PAPP-A and C-peptide in the GDM group were independent risk factors for neonatal hypoglycemia. Serum Lp-PLA2, PAPP-A and C-peptide of GDM patients had certain predictive value for the occurrence of neonatal hypoglycemia, among which C-peptide had the greatest predictive value. Conclusion:High levels of serum Lp-PLA2, PAPP-A and C-peptide are independent risk factors for neonatal hypoglycemia in GDM patients, and have certain predictive value, which can provide a reference for clinical prediction of its occurrence.

Efficiency of preeclampsia screening based on biomarkers of aneuploidy screening in first trimester / 中华围产医学杂志

Objective:To evaluate the performance of biomarkers in aneuploidy screening in the first trimester-pregnancy associated plasma protein A(PAPP-A) combined with Fetal Medicine Foundation (FMF)'s competing risk model in screening preeclampsia among our population.Methods:This study was based on a prospective cohort of singleton pregnant women who underwent aneuploidy screening in the first trimester in Nanjing Drum Tower Hospital from January 2017 to September 2020. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and PAPP-A were converted into multiples of median (MoM) using the algorithm disclosed on the website of the FMF (fetalmedicine.org). The predictive outcomes of maternal factors alone or in combination with MAP, UtA-PI, and PAPP-A (alone or in combination) were calculated. Chi-square test, Fisher's exact test or rank sum test were used for comparison among groups and Bonferroni method for pairwise comparisons. Receiver operating characteristic (ROC) curve was used to evaluate the screening efficiency and to calculate the sensitivities of predicting preeclampsia, term and preterm preeclampsia at false-positive rates of 5% and 10%. The predictive performance of this model was further compared to the screening strategy that was recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China (2020). Results:Among the 5 144 singleton pregnancy women who were recruited in the cohort, 4 919 cases were included and analyzed in this study. A total of 223 cases were diagnosed as preeclampsia (4.5%), including 55 preterm (1.1%) and 168 term preeclampsia (3.4%). The median of MoM values of MAP, UtA-PI, and PAPP-A in the non-preeclampsia group were around 1.0±0.1. Statistical significance was observed in the difference of MAP, UtA-PI, and PAPP-A Mom between women with preterm preeclampsia and those without preeclampsia [1.061 (0.999-1.150) vs 0.985 (0.935-4.043), 1.115 (0.873-1.432) vs 1.039 (0.864-1.236), 0.820 (0.493-1.066) vs 1.078 (0.756-1.508)], which was also seen in the difference of MAP and PAPP-A Mom between women with term preeclampsia and those without preeclampsia [1.065 (1.002-1.133) vs 0.985 (0.935-4.043), 1.007 (0.624-1.393) vs 1.078 (0.756-1.508)] (all P<0.025). The combination screening with maternal factors+MAP+UtA-PI+PAPP-A was noted for the best efficiency. In predicting preeclampsia preterm and term preeclampsia at the false-positive rate of 10%, the sensitivity of the model was 53.0%, 76.4% and 44.6% respectively. Using the screening method recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020), the proportion of people at high risk of preeclampsia was 5.9% (290/4 919), and the sensitivity for predicting preterm preeclampsia was 25.5% (14/55), which was significantly lower than the combination screening with maternal factors+MAP+UtA-PI+PAPP-A [65.5% (36/55)] when using the same proportion of high-risk population. Conclusion:The preeclampsia screening model based on aneuploidy screening biomarkers in the first trimester--PAPP-A in combination with materral factors, MAP, UtA-PI, can effectively screen preterm preeclampsia in the local population without increasing the laboratory costs.

The role of pregnancy-associated plasma protein-a level in the first trimester of pregnancy and clinical outcome in an urban referral centre

Background: Estimation of serum PAPP-A levels studied predictability for adverse perinatal outcome. This case control study tries to establish the association between low PAPP-A levels among the pregnant woman and adverse maternal foetal outcome.Methods: This is an case-control study during 2017-2018 in the women delivered at Department of OBG at Mehta Hospitals. Women delivered in the labour room  had a first trimester screening of PAPP-A level were explained, taken informed consent, questionnaire which include detailed antenatal history, mode of delivery and baby data.  Depending upon outcome, the subjects are classified as case group or control group, out of the study sample of 264 subjects, 88 patients who had complications were taken as cases and 176 patients with no complications taken as control were undertaken.Results: Low PAPP-A level (<0.5 MoM) showed high incidence of PIH and preeclampsia, followed by IUGR and Preterm. PAPP-A level >0.5 MoM, normal outcome is more than the adverse outcome. The difference in the PAPP-A levels is statistically significant. In women with low PAPP A level, low birth weight found statistically significant when compared with <0.5 PAPP A level. The sensitivity of PAPP A levels in identifying the complicated outcomes was 17.04%.The specificity was 98.85%. The positive predictive value of predicting the complications was 88.23% and negative predictive value of 70.44%.Conclusions: The low PAPP-A levels confirmed during first trimester of pregnancy is associated with adverse maternal and foetal outcome such as PIH, preeclampsia, preterm, IUGR and LBW.

Role of pregnancy associated plasma protein-A and doppler velocimetry in the assessment of fetomaternal outcome in high risk pregnancy

Background: The study aimed at defining the role of Pregnancy associated plasma protein-A (PAPP-A) and uterine artery doppler (Ut.A.PI) in the development of adverse pregnancy outcome (APO) in high risk pregnancies.Methods: This was an observational study where 100 singleton pregnancies at high risk of development of APO, between 11 to 13 + 6 weeks POG were enrolled. PAPP-A levels were measured at 11 to 13 + 6 weeks POG and uterine artery doppler PI was measured at 20 weeks. Women were followed till delivery. Pregnancy outcome were seen and a cut off at which APO developed was derived.Results: In this study women with lower mean PAPP-A (0.75±0.19 MOM versus 1.23±0.31MOM) (p<0.001) values and higher Ut.A.PI (1.43±0.35MOM versus 0.99±0.25MOM) (p<0.001) developed APO. Cut off value for PAPP-A and Ut.A.PI was determined and was found to be ≤11.65 µg/ml (≤0.79MoM) and   >1.42 (>1.19MoM) respectively which was higher than what is determined in other studies done on low risks populations thereby suggesting for an intervention or more meticulous observations at a higher cut offs.Conclusions: PAPP-A and uterine artery doppler are already being used for the screening of preeclampsia in most of the countries but not for other adverse pregnancy outcomes. PAPP-A levels along with the uterine artery PI in predicting APO in high risk women has high negative predictive value. Hence can be uses as a screening method in high risk population whether they should be used for low risk population also needs further evaluation.

First-trimester combined screening test for aneuploidies in brazilian unselected pregnancies: diagnostic performance of fetal medicine foundation algorithm / Rastreio combinado do primeiro trimestre para aneuploidias em gestantes brasileiras não selecionadas: desempenho diagnóstico do algoritmo da Fetal Medicine Foundation

Abstract Objective The main objective of this study was to examine the diagnostic performance of the first-trimester combined test for aneuploidies in unselected pregnancies from Rio de Janeiro and compare it with the examples available in the literature. Methods We investigated 3,639 patients submitted to aneuploidy screening from February 2009 to September 2015. The examination is composed of the Fetal Medicine Foundation risk evaluation based on nuchal translucency evaluation, mother's age, presence of risk factors, presence of the nasal bone and Doppler of the ductus venous in addition to biochemical analysis of pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG) markers. The cut-off point for high risk for aneuploidies was defined as greater than 1:100, with intermediate risk defined between 1:100 and 1:1,000, and low risk defined as less than 1:1,000. The variable aneuploidy was considered as a result not only of trisomy of chromosome 21 but also trisomy of chromosomes 13 and 18. Results Excluding the losses, the results of 2,748 patients were analyzed. The firsttrimester combined test achieved 71.4% sensitivity with a 7.4% false-positive (FP) rate, specificity of 92.6%, positive predictive value (PPV) of 6.91% and negative predictive value (NPV) of 99.76%, when the cut-off point considered was greater than 1:1,000. Through a receiving operating characteristics (ROC) curve, the cut-off point that maximized the sensitivity and specificity for the diagnosis of aneuploidies was defined as 1:1,860. When we adjusted the false-positive (FP) rate to 5%, the detection rate for this analysis is 72.7%, with a cut-off point of 1:610. Conclusion The combined test of aneuploidy screening showed a detection rate inferior to those described in the literature for a higher FP rate.

Resumo Objetivo O objetivo principal deste estudo foi examinar o desempenho diagnóstico do rastreio combinado de aneuploidias do primeiro trimestre em gestações não selecionadas do Rio de Janeiro e compará-lo com os exemplos disponíveis na literatura. Métodos Investigamos 3.639 pacientes submetidas à triagem para aneuploidia, de fevereiro de 2009 a setembro de 2015. O exame é composto pela avaliação do risco da FetalMedicine Foundation combase na avaliação da translucência nucal, idade da mãe, presença de fatores de risco, presença de osso nasal e Doppler do ducto venoso, além da análise bioquímica dos marcadores proteína A plasmática associada à gravidez (PAPP-A) e gonadotrofina coriônica humana-beta (β-hCG). O ponto de corte para alto risco de aneuploidias foi definido como superior a 1:100, para risco intermediário foi definido entre 1: 100 e 1: 1.000 e para baixo risco foi definido como inferior a 1:1.000. A variável aneuploidia foi considerada não apenas como resultado da trissomia do cromossomo 21, mas também da trissomia dos cromossomos 13 e 18. Resultados Excluindo as perdas, foram analisados os resultados de 2.748 pacientes. O teste combinado do primeiro trimestre alcançou 71,4% de sensibilidade com uma taxa de falsos positivos (FPs) de 7,4%, especificidade de 92,6%, (valor preditivo positivo) VPP de 6,91% e (valor preditivo negativo) VPN de 99,76%, quando o ponto de corte considerado foi maior que 1:1.000. Através de uma curva de característica de operação do receptor (COR), o ponto de corte que maximizou a sensibilidade e especificidade para o diagnóstico de aneuploidias foi de 1:1.860. Quando corrigimos a taxa de FP para 5%, a taxa de detecção para esta análise é de 72,7%, com um ponto de corte de 1:610. Conclusão O rastreio combinado de aneuploidia mostrou uma taxa de detecção inferior à descrita na literatura para uma maior taxa de FP.

Low maternal serum pregnancy-associated plasma protein-A as a risk factor of preeclampsia

<p><b>INTRODUCTION</b>Low levels of pregnancy-associated plasma protein-A (PAPP-A) might be associated with abnormal placentation, leading to the development of preeclampsia during late gestation. We aimed to determine the association between low serum PAPP-A levels and rates of preeclampsia in Thai women with otherwise low-risk pregnancies.</p><p><b>METHODS</b>A cohort study was conducted on consecutive singleton pregnancies undergoing first trimester screening for fetal Down syndrome at a tertiary centre hospital. A prospective database was assessed for patient records, including PAPP-A levels, pregnancy outcomes and obstetrics complications. Pregnancies with potential causes of preeclampsia were excluded. Enrolled women were categorised into two groups: women with normal PAPP-A levels (≥ 10th percentile; control group); and those with low PAPP-A levels (< 10th percentile; study group). The main outcome measure was rate of preeclampsia.</p><p><b>RESULTS</b>Of 6,887 women screened, 3,830 were available for analysis and 167 were excluded due to potential confounders. Of the remaining 3,663 women enrolled, 357 women were categorised as having low PAPP-A levels and 3,306 had normal PAPP-A levels. The prevalence of preeclampsia (8.4% vs. 2.6%) and early-onset preeclampsia (i.e. before 34 weeks of gestation) (1.1% vs. 0.1%) was significantly higher (relative risk 3.27 and 9.26, respectively) in women from the study group than in the control group.</p><p><b>CONCLUSION</b>Pregnancy with PAPP-A levels < 10th percentile was significantly associated with an increased risk of preeclampsia that tended toward early development. Therefore, pregnant women with low PAPP-A levels in the first trimester should be considered to be at increased risk of preeclampsia.</p>

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.

Updates on the relationship between PAPP-A2 and fetus disease / 国际儿科学杂志

Pregnancy-associated plasma protein-A2(PAPP-A2)is a metalloproteinase,which expresses in many tissues and cells,especially in maternal serum and placenta.PAPP-A2 plays an important role in the em-bryonic growth and development. Abnormal PAPP-A2 levels are associated with pre-eclampsia,Down's syn-drome,developmental dysplasia of the hip and other diseases,but the specific mechanism is still unclear.The mo-lecular structure and function of PAPP-A2,the research advances in the relationship between PAPP-A2 and fetus disease are reviewed in this paper.

Risk assessment for preeclampsia by biochemical and biophisycal markers at first trimester / Монголын Анагаах Ухаан

Introduction@#Preeclampsia, which affects about 2-8% of pregnancies, is major cause of maternal and perinatal morbidity and mortality, particularly in developing countries. In Mongolia, preeclampsia and eclampsia occurred among pregnancy complications about 25% in recent years. There is a percentage for a cause of maternal death was 17.7% in preeclampsia and eclampsia between 2012 and 2015 in Mongolia.</br> Effective prediction of preeclampsia can be achieved at 11-13 week’s gestation by combination of maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A).@*Goal@#To investigate plasma concentration of PIGF and PAPP-A, in pregnant women at 11-13+6 of gestation for screening of preeclampsia, To examine the performance of first-trimester screening for preeclampsia based on maternal characteristics, MAP, and mUt.A-PI.@*Materials and Methods @#The study conducted among 393 single pregnant women at 11-13+6 weeks, who were visiting antenatal care services, between March, 2015 and June, 2017. The prospective Cohort research method was used for this study. Written informed consent was obtained from all participants. Maternal plasma PAPP-A, PlGF were determined using Perkin Elmer kits by fluoroimmunoassay.</br> Measurement of MAP was by validated automated devices (HEM-7120, Оmron, Japan). MAP was calculated from the formula DP + 1/3*(SP-DP), where DP represents diastolic blood pressure and SP- systolic blood pressure. Trans-abdominal ultrasound (Voluson E8, GE, USA) examination was carried out for Ut.A-PI.@*Results@#In the study population, there were 66 (16.8%) cases that experienced preeclampsia and 327 (83.2%) cases that were unaffected by preeclampsia. The result showed that the mean concentration of PlGF was 38.6±19.6 pg/ml in PE group whereas the mean was 45.1±24.0 pg/ml in normal pregnant women. Level of PAPP-A was 366.1±195.3 mU/L in group with PE, 633.6±496.9 mU/L in group without preeclampsia. </br> The best Youden’s index and area under the curve (AUC) for MAP and mUt.A-PI were as a predictor of PE. It can be shown that the cutoff point for MAP was 89.5 mmHg (sensitivity-71.2%; specificity-75.5% J-0.467; AUC-0.792; P<0.001). The cutoff point of mUt.A-PI was 2.34 (sensitivity-33.3%; specificity-77.7% J-0.12; AUC-0.577; P<0.001).@*Conclusions@#The concentration of PIGF and PAPP-A in pregnant women with preeclampsia at 11-13+6 of gestation was lower than normal pregnant women. The detection risk of PE by MAP is more accurate than the mUtA-PI measurement.

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.

Study the significance of blood VEGF,PAPP-A,D-D and urinary NAG/Cr ratio in patients with PIH / 国际检验医学杂志

Objective To study the clinical significance of changes of blood contents of vascular endothelial growth factors (VEGF).Pregnancy-associated plasma protein-A(PAPP-A),D-dimers(D-D)and Urinary N-acetyl-β-D-glucosaminidase/Creatinine (NAG/Cr)Ratio in patients with Pregnancy Induced Hypertension syndrome(PIH).Methods Serum VEGF and PAPP-A(with ELISA),plasma D-dimers(with biochemistry)and NAG/Cr(with velocity)contents were measured in 92 pregnant women with PIH and 35 controls.Results The serum VEGF contents in patients with PIH were significantly lower than those in controls(P<0.01)while PAPP-A,D-dimers and NAG/Cr contents were significantly higher(P<0.01).Those changes were especially marked in patients with advanced diseases.Conclusion Changes of blood contents of VEGF,PAPP-A D-dimers and Urinary NAG/Cr Ratio were closely related with the disease process of PIH.Determination of these changes was of clinical diagnostic as well as prognostic value.

Effect of Simvastatin on Plasma Malondialdehyde LDL (MDA-LDL) and Pregnancy-Associated Plasma Protein (PAPP-A) in Patients of Coronary Heart Disease / 中华高血压杂志

Objective To examine plasma levels of MDA-LDL and pregnancy-associated plasma protein-A in patients with angiography type lesions Ⅱ(representing plaque rupture with or without thrombosis), and to evaluate the effect of simvastatin on plasma MDA-LDL and PAPP-A. Methods One hundred and ten patients were enrolled and underwent coronary angiography with 85 patients diagnosed as coronary heart disease (CHD) and twenty-five as controls. According to the morphologic types of plaque, the patients with CHD were straitified as type Ⅰ(smooth borders) (n=31) and type Ⅱ(irregular lesions) (n=35) and type Ⅲ (long lesions with irregular surface) group (n=19). The patients in type Ⅱ group received simvastatin (40 mg/d ) for four weeks. The plasma MDA-LDL, PAPP-A, LDL, HDL levels before and after simvastatin treatment were determined. Results Plasma levels of MDA-LDL, PAPP-A in type Ⅱ group was significantly higer than that in the controls group, type Ⅰ group, type Ⅲ group (P

Increased Activity of Insulin-like Growth Factor binding Protein-4 Protease in H-mole Patients / 대한내분비학회지

BACKGROUND: Hydatidiform mole (H-mole) is characterized by the neoplastic proliferation of trophoblasts. Only 1~10% of patients with partial H-mole will develop a trophoblastic tumor, but 18~29% of those with complete H-mole will develop a persistent trophoblastic tumor. Therefore, the early diagnosis and monitoring after operation of an H-mole disease are very important. Recently, the pregnancy associated plasma protein-A (PAPP-A) was proved to have a similar role as that of IGF binding protein-4 (IGFBP-4) protease, which has shown an increasing function in fetal growth and development by degradation of IGFBP-4 and an increase in IGF in the serum during pregnancy. Our hypothesis is "the H-mole, which shows placental hyperplasia will also have an IGFBP-4 protease activity, which may be used as in the early diagnosis and monitoring of H-mole disease". METHODS: Serum samples from 6 non-pregnant, 18 pregnant (5 in the 1st trimester, 10 in the 2nd, and 3 in the 3rd), 12 postpartum women and 3 H-mole patients(2 with complete H-mole and 1with partial H-mole) were collected and measured for the -HCG, IGF and PAPP-A levels and IGFBP-4 protease activities by a IGF-II ligand blot analysis and electrophoresis method. The IGFBP-4 protease activity of the serum during normal pregnancy was compared with that of H-mole disease. RESULTS: The results from the in vitro protease assays using recombinant IGFBP-4 determined that IGFBP-4 proteolysis was significantly increased during the first (56%) and second trimesters (90%), but reached a plateau by the third trimester (94%). In H-mole disease diagnosed 11 weeks after conception, the IGFBP-4 proteolytic activity was 97%, which was nearly the same as at terminal pregnancy. This activity gradually decreased to 75% at 1 week, 58.7% at 2 and 33% at 3 weeks after the operation. The -HCG was also decreased from 490,400 to 123,822.7, 1,352.3, and 128.5 mIU/mL at 1, 2 and 3 weeks after the operation, respectively. The PAPP-A level also gradually decreased from 34.87 to 25.5, 12.0 and 2.7 g/mL 1, 2 and 3 weeks after the operation, respectively. However, the IGF decreased from 238.3 to 172.9 ng/mL 1 week after the operation, but increased to 251.4 and 295 ng/mL at 2 and 3 weeks after the operation, respectively. CONCLUSION: These results demonstrated that the IGFBP-4 protease activity was significantly increased during pregnancy, and was extremely elevated durimg the early stages of H-mole disease, but gradually decreased after removal of molar tissue. Therefore, measuring the IGFBP-4 protease activity may play an important role in the early diagnosis and monitoring of H-mole disease

Increased Activity of Insulin-like Growth Factor binding Protein-4 Protease in H-mole Patients / 대한내분비학회지

BACKGROUND: Hydatidiform mole (H-mole) is characterized by the neoplastic proliferation of trophoblasts. Only 1~10% of patients with partial H-mole will develop a trophoblastic tumor, but 18~29% of those with complete H-mole will develop a persistent trophoblastic tumor. Therefore, the early diagnosis and monitoring after operation of an H-mole disease are very important. Recently, the pregnancy associated plasma protein-A (PAPP-A) was proved to have a similar role as that of IGF binding protein-4 (IGFBP-4) protease, which has shown an increasing function in fetal growth and development by degradation of IGFBP-4 and an increase in IGF in the serum during pregnancy. Our hypothesis is "the H-mole, which shows placental hyperplasia will also have an IGFBP-4 protease activity, which may be used as in the early diagnosis and monitoring of H-mole disease". METHODS: Serum samples from 6 non-pregnant, 18 pregnant (5 in the 1st trimester, 10 in the 2nd, and 3 in the 3rd), 12 postpartum women and 3 H-mole patients(2 with complete H-mole and 1with partial H-mole) were collected and measured for the -HCG, IGF and PAPP-A levels and IGFBP-4 protease activities by a IGF-II ligand blot analysis and electrophoresis method. The IGFBP-4 protease activity of the serum during normal pregnancy was compared with that of H-mole disease. RESULTS: The results from the in vitro protease assays using recombinant IGFBP-4 determined that IGFBP-4 proteolysis was significantly increased during the first (56%) and second trimesters (90%), but reached a plateau by the third trimester (94%). In H-mole disease diagnosed 11 weeks after conception, the IGFBP-4 proteolytic activity was 97%, which was nearly the same as at terminal pregnancy. This activity gradually decreased to 75% at 1 week, 58.7% at 2 and 33% at 3 weeks after the operation. The -HCG was also decreased from 490,400 to 123,822.7, 1,352.3, and 128.5 mIU/mL at 1, 2 and 3 weeks after the operation, respectively. The PAPP-A level also gradually decreased from 34.87 to 25.5, 12.0 and 2.7 g/mL 1, 2 and 3 weeks after the operation, respectively. However, the IGF decreased from 238.3 to 172.9 ng/mL 1 week after the operation, but increased to 251.4 and 295 ng/mL at 2 and 3 weeks after the operation, respectively. CONCLUSION: These results demonstrated that the IGFBP-4 protease activity was significantly increased during pregnancy, and was extremely elevated durimg the early stages of H-mole disease, but gradually decreased after removal of molar tissue. Therefore, measuring the IGFBP-4 protease activity may play an important role in the early diagnosis and monitoring of H-mole disease

The efficacy of nuchal translucency with free beta-hCG, PAPP-A as a screening test for detection of chromosomal anomaly in the first trimester of pregnancy / 대한산부인과학회잡지

OBJECTIVES: The aim of this study is to determine the efficacy of nuchal translucency in combination with free beta-hCG, PAPP-A in the first trimester screening for chromosomal anomaly in general population. METHODS: Between April 1998 and December 1999, we evaluated 263 pregnant women undergoing first trimester screening test for fetal chromosomal anomaly using nuchal translucency combined with free beta-hCG, PAPP-A. We confirmed the pregnancy outcomes through chorionic villi sampling, amniocentesis or term delivery. We excluded 15 pregnant women because of their obscure pregnancy outcomes. Statistical analysis was considered significant when P value was lower than 0.05. RESULTS: With a risk cut-off of 1 in 400, 24 pregnancies(9.7%) of 248 cases were screen positive and 224 pregnancies(90.3%) were screen negative. 2 cases of Down syndrome and 1 case of Turner syndrome were detected in screen positive group. No chromosomal anomalies were detected in screen negative group. CONCLUSION: In this study, 8.57% of false positive rate and 12.5% of positive predictive value were obtained in the first trimester screening for chromosomal anomaly using nuchal translucency and serum markers.

Evaluation of the Dual Test using PAPP-A and Free beta-hCG in First Trimester as a Prenatal Screening Test for Down Syndrome / 대한임상병리학회지

BACKGROUND: Dual test has been reported to be a useful first trimester screening test for Down syndrome and is comprised of measuring two serum parameters; pregnancy associated plasma protein A(PAPP-A) and free beta chorionic gonadotrophin(beta-hCG). This study was performed to investigate the distribution of these two parameters in Korean pregnant women and compare its significance with that of Triple test which is a second trimester screening test and being more commonly used in Korea. METHODS: For the Dual test, serum PAPP-A and free beta-hCG were each measured by radioimmunoassay(AMERLEX-M kitTM) in 2,526 first-trimester pregnant women. Triple test was done in 7,007 second-trimester pregnant women. RESULTS: The median value of PAPP-A was 9.3, 12.5, 18.1 and 26.6 IU/mL, and that of free beta-hCG was 47.8, 35.4, 29.4 and 29.3 nmol/L in 10th, 11th, 12th and 13th gestational week, respectively. The Dual test was positive in 7.8%(198/2,526), while the Triple test was positive in 3.0%(208/7,007). Among 87 Dual test positive cases, Down syndrome was diagnosed in three cases(3.5%), while 71 Triple test positive cases, seven cases(9.9%) were Down syndrome. Among 1,316 cases who had both the Dual and Triple test, 1,300(98.8%) were both negative, and two(0.2%) were both positive, showing 99% of concordance rate. CONCLUSIONS: These results showed a possibility that the Dual test could be used as a valuable first-trimester screening test for Down syndrome in our country.