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.
Pre-Eclampsia ; Pregnancy-Associated Plasma Protein-A

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.
Chorion ; Down Syndrome* ; Female ; Humans ; Korea ; Mass Screening ; Plasma ; Pregnancy ; Pregnancy Trimester, First* ; Pregnancy Trimester, Second ; Pregnancy-Associated Plasma Protein-A* ; Pregnant Women ; Prenatal Diagnosis*

Prenatal diagnosis of Down syndrome requires an invasive test in women considered to be at high risk after screening. At present, there are variable screening tests. For a 5% false-positive rate, the sensitivities are approximately 20-30% for maternal age alone, 60-70% for maternal age and second-trimester maternal serum markers, 85% for maternal age with fetal nuchal translucency and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks, and 94% for maternal age with fetal nuchal translucency and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks following second-trimester maternal serum markers. This article examines the studies of screening for Down syndrome and summarizes the results from major studies reporting on the implementation of this method.
Biomarkers ; Chorionic Gonadotropin ; Down Syndrome* ; Female ; Humans ; Mass Screening ; Maternal Age ; Nuchal Translucency Measurement ; Pregnancy-Associated Plasma Protein-A ; Prenatal Diagnosis*

OBJECTIVETo 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.

METHODSPatients 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.

RESULTSCompared 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).

CONCLUSIONIn the early phase of ACS attack, the elevation of PAPP-A is an independent risk factor for the occurrence of cardiovascular adverse events.

Acute Coronary Syndrome ; blood ; diagnosis ; Aged ; Female ; Humans ; Male ; Middle Aged ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prognosis ; Risk Factors

Fetal nuchal translucency (NT) is an echolucent space between the dorsal edge of soft tissue of the fetal neck and the linear echo of the skin observed in a midsagittal image measured at 11 to 13(+6) weeks of gestation. Increased NT (>95 percentile) is highly associated with fetal aneuploidy and congenital structural anomalies including congenital heart defects. In combination with maternal serum PAPP-A and free beta-hCG, increased NT has been demonstrated to provide efficient Down syndrome risk assessment, with a detection rate of 80-87% (5% false-positive rate), and it also allows earlier diagnosis of fetal aneuploidy. Even in the absence of aneuploidy, increased NT is still associated with an increase in adverse perinatal outcome including abortion, fetal death and a variety of fetal malformations. This paper will review the mechanism of increased NT, correct measurement of NT, and recent evidences for interpretation and management for the fetuses with increased NT.
Aneuploidy ; Down Syndrome ; Fetal Death ; Fetus ; Heart Defects, Congenital ; Neck ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy-Associated Plasma Protein-A ; Risk Assessment ; Skin

OBJECTIVESerum pregnancy-associated plasma protein A (PAPP-A) is increased in acute coronary syndrome patients and related to prognosis. We investigated the effects of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) on PAPP-A mRNA expression in monocytes.

METHODSMonocytes were isolated by Ficoll density gradient centrifugation from blood of healthy volunteers. The PAPP-A expressions at mRNA level post CRP or rhTNF-alpha stimulation were measured by RT-PCR.

RESULTSPAPP-A mRNA expression in peripheral blood monocytes increased 2 hours (0.2128 +/- 0.0136) and peaked 24 hours (0.6837 +/- 0.1360) after CRP (20 mg/L) stimulation compared with control group (0.1842 +/- 0.0101). PAPP-A mRNA expression increased rapidly, peaked 2 hours (1.2546 +/- 0.0866) and remained elevated up to 24 hours (0.8203 +/- 0.0413) after rhTNF-alpha (100 ng/ml) stimulation. The effects of CRP and TNF-alpha were dose-dependent. PAPP-A mRNA expression of monocytes were 0.2544 +/- 0.0611, 0.4177 +/- 0.1200, 0.5828 +/- 0.0152, 0.6837 +/- 0.1360 after stimulated with CRP (1, 5, 10, 20 mg/L), and 0.2424 +/- 0.1378, 0.3335 +/- 0.0196, 0.5742 +/- 0.0131, 0.6913 +/- 0.0219 and 0.8203 +/- 0.0413 after stimulated with rhTNF-alpha (5, 10, 25, 50 and 100 ng/ml). Actinomycin D, the DNA-directed RNA polymerase inhibitor, completely blocked CRP and TNF-alpha induced PAPP-A expression.

CONCLUSIONSPAPP-A mRNA expression could be stimulated by CRP and TNF-alpha in human peripheral blood monocytes which might be responsible for the increased serum PAPP-A level in patients with acute coronary syndromes.

C-Reactive Protein ; adverse effects ; pharmacology ; Cells, Cultured ; Humans ; Monocytes ; drug effects ; metabolism ; Pregnancy-Associated Plasma Protein-A ; metabolism ; RNA, Messenger ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology

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.
Chorionic Gonadotropin ; Chromosome Aberrations* ; Crown-Rump Length ; Diagnostic Tests, Routine ; Down Syndrome ; Female ; Fetus ; Genetic Counseling ; Gestational Age ; Humans ; Korea ; Mass Screening* ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, First* ; Pregnancy* ; Pregnancy-Associated Plasma Protein-A ; Prenatal Diagnosis ; Trisomy

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.
Chorionic Gonadotropin ; Chromosome Aberrations* ; Crown-Rump Length ; Diagnostic Tests, Routine ; Down Syndrome ; Female ; Fetus ; Genetic Counseling ; Gestational Age ; Humans ; Korea ; Mass Screening* ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, First* ; Pregnancy* ; Pregnancy-Associated Plasma Protein-A ; Prenatal Diagnosis ; Trisomy

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.
Amniocentesis ; Biomarkers ; Chorionic Villi Sampling ; Down Syndrome ; Female ; Humans ; Mass Screening* ; Nuchal Translucency Measurement* ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, First* ; Pregnancy* ; Pregnancy-Associated Plasma Protein-A* ; Pregnant Women ; Turner Syndrome

OBJECTIVESTo 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.

METHODSThe 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.

RESULTSSerum 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.

CONCLUSIONSThere 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.

Aged ; Aged, 80 and over ; CD40 Ligand ; blood ; Carotid Stenosis ; blood ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Pregnancy-Associated Plasma Protein-A ; metabolism