Value Analysis of Four-Dimensional Color Ultrasound Combined with Maternal Serological Index in Prenatal Screening for Fetal Anomalies.

Objective: This study aimed to assess the efficacy of combining four-dimensional (4D) color ultrasound with maternal serological index testing in prenatal screening for fetal anomalies. Methods: A retrospective analysis was conducted on data from 864 pregnant women who underwent prenatal checkups at the hospital between January 2020 and January 2021. During the mid-pregnancy period, serological tests were performed to determine levels of alpha-fetoprotein (AFP), free ß-subunit of human chorionic gonadotropin (Free-HCG ß), pregnancy-associated plasma protein A (PAPP-A), and vitamin B12 (VitB12). Additionally, 4D color ultrasound examinations were conducted. The gold standard for evaluation was the results of delivery or labor induction. AFP, Free-HCG ß, PAPP-A, and VitB12 levels were compared between the anomaly group and the normal group. The diagnostic efficacy of single and combined detection of serological indexes and 4D color ultrasound was analyzed, with the calculation of the areas under the curve (AUC) for different detection methods. Results: Among the 864 pregnant women, 44 cases (5.09%) exhibited fetal anomalies, while 820 cases (94.91%) did not. The anomaly group showed significantly higher multiples of the median (MOM) values for AFP and Free-HCG ß (P < .001) and significantly lower PAPP-A MOM and VitB12 levels (P < .001) compared to the normal group. The sensitivity of single detections for AFP MOM, Free-HCG ß MOM, PAPP-A MOM, VitB12, 4D color ultrasound, and combined detection were 63.64%, 68.18%, 65.91%, 54.55%, 77.27%, and 97.93%, respectively. The corresponding AUC values were 0.805, 0.829, 0.818, 0.761, 0.885, and 0.974. Conclusions: The combination of 4D color ultrasound with maternal serological index testing demonstrated high sensitivity in prenatal screening for fetal anomalies.

Can serum ferritin, vitamin B(12) and folic acid levels affect serum screening tests during pregnancy?

OBJECTIVE: To examine the relation of serum folate, vitamin B(12) and ferritin levels to 1st and 2nd trimester serum screening markers. METHODS: Fetal crown-rump length (CRL), nuchal translucency (NT), and first and second trimester serum screening tests of 228 pregnant women were obtained. In all cases, serum vitamin B(12), folic acid and ferritin levels were analyzed during the 11-14 week period. Levels below <15 µg/L, 3 ng/mL and 211 pg/mL were accepted as nutrient deficiency for serum ferritin, folic acid and vitamin B(12), respectively. Results of serum screening markers of women below and above these values were compared with each other. RESULTS: Comparison of groups with ferritin levels <15 and >15 µg/L for 1st and 2nd trimester serum screening parameters revealed significant differences between groups in terms of pregnancy associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (fb-hCG), AFP and hCG. Comparison of women with low versus normal B(12) levels revealed significant differences in terms of NT, PAPP-A and fb-hCG. CONCLUSION: Although sufficient, number of cases is limited in this study so results cannot be generalized to all population. It could be advised that in addition to folic acid supplementation, deficiencies of ferritin and B(12) must be corrected in patients considering pregnancy or early 1st trimester pregnant women to obtain more accurate serum screening results.

[Modern methods of early screening for preeclampsia and pregnancy-induced hypertension--a review]. / Wspólczesne metody wczesnej diagnostyki stanu przedrzucawkowego i nadcisnienia indukowanego ciaza.

Preeclampsia remains to be a serious perinatal complication and early screening for this disease to identify the high risk population before the first symptoms develop constitutes a considerable clinical challenge. Modern methods of screening for preeclampsia and pregnancy-induced hypertension include patients history biochemical serum markers and foetal DNA and RNA in maternal serum. They aid the process of developing an optimal protocol to initiate treatment in early pregnancy and to reduce the rate of complications. Our review presents an overview of the novel methods and techniques used for early screening for preeclampsia and pregnancy-induced hypertension. Most of the research focuses on 11-13 weeks of gestation due to the fact that the first prenatal examination is performed at that time. The most important information seems to be: weight, mass, mean blood pressure, history of pregnancy-induced hypertension or preeclampsia at previous pregnancies as well as the ethnic origin. During an ultrasound scan, pulsatility index of the uterine arteries is measured. Blood samples are obtained during the last part of the examination. At the moment only a few markers seem to be strong predictors of hypertensive disorders during pregnancy: pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Also, fetal DNA and RNA in maternal plasma are helpful in the prediction of preeclampsia as they are markers of the trophoblast apoptosis. Researchers aim at identifying the population at high risk of pregnancy-induced hypertension and preeclampsia in order to offer appropriate antenatal care to these women. At the moment many drugs and diet supplements are investigated to reduce the prevalence of hypertensive disorders in pregnancy. These medications are usually administrated in early gestation (up to 16 week of gestation) before the first clinical symptoms present. Low doses of aspirin were found to decrease the risk of preeclampsia in high-risk groups. Moreover, according to some recent research, also essential omega-3 fatty acids reduce the incidence of preeclampsia. None of the other investigated diet supplements or antioxidants were proven to successfully reduce incidents of hypertensive disorders. So far, there is available evidence on the lack of any effect for vitamines C, D or E. Further studies are necessary to define clinical useful markers of gestational hypertension.

Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease.

BACKGROUND: Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. OBJECTIVES: In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n = 563, age 70+/-6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. RESULTS: Smokers had significantly higher levels of MMP-9 (p<0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p<0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP-9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. CONCLUSIONS: The elevated levels of MMP-9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP-9, TIMP-1 or PAPP-A in the present population.

Pregnancy-associated plasma protein-A elevation in patients with acute coronary syndrome and subsequent atorvastatin therapy.

Pregnancy-associated plasma protein-A (PAPP-A) was associated with atherosclerotic plaque vulnerability, whereas statin therapy was associated with increased plaque stability. Eighty-six patients presenting with clinical indications (non-ST-elevation myocardial infarction, unstable angina, and stable angina) for invasive coronary angiography and subsequent verified coronary artery disease (CAD) were randomly assigned in a double-blind manner to atorvastatin 10 or 80 mg/day. PAPP-A, high-sensitivity C-reactive protein (hs-CRP), and lipids were measured at baseline (before statin therapy) and at 1 and 6 months. PAPP-A was significantly increased in 35 patients with acute coronary syndrome (ACS) compared with 51 patients with stable CAD (p <0.001). Patients randomly assigned to atorvastatin 10 mg did not show a significant decrease in PAPP-A from baseline at 1 or 6 months. Patients treated with atorvastatin 80 mg showed a significant decrease at 1 month compared with baseline, but not at 6 months. hs-CRP was not significantly different between the ACS and stable CAD groups. Patients receiving atorvastatin 10 mg showed no hs-CRP decrease at 1 or 6 months, whereas it significantly decreased in the 80-mg group at 6 months, but not at 1 month. In conclusion, PAPP-A significantly increased in patients with ACS compared with those with stable coronary disease. High-dose atorvastatin significantly decreased PAPP-A at 1 month and hs-CRP at 6 months in patients with verified CAD. Low-dose atorvastatin did not produce this effect.

Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients.

BACKGROUND: The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. METHODS: 29 HD patients were randomized into two groups: 15 patients were treated orally with 400 mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical--TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. RESULTS: Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23+/-11.94 vs. 11.41+/-1.94 mIU/L, p<0.001; CRP: 5.20+/-3.50 vs. 3.40+/-3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. CONCLUSION: Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.

Long term influence of regular intake of high dose n-3 fatty acids on CD40-ligand, pregnancy-associated plasma protein A and matrix metalloproteinase-9 following acute myocardial infarction.

Pregnancy-associated plasma protein A (PAPP-A) and matrix metalloproteinase 9 (MMP-9), both zinc-binding endopeptidases, are abundantly expressed in ruptured and eroded plaques in patients with acute coronary syndromes (ACS). The adhesion molecule CD-40 ligand (CD40L), expressed on activated platelets and T-lymphocytes, can activate metalloproteinases and thereby promote plaque-rupture. N-3 fatty acids, through their anti-inflammatory and anti-thrombotic properties, might reduce the levels of these proatherosclerotic markers and thereby the development of ACS. 300 patients were randomized on day 4 to 6 following an acute myocardial infarction (MI) to receive either 4 g of n-3 fatty acids or a similar daily dose of corn oil for at least one year. We compared levels of PAPP-A, MMP-9 and sCD-40 L at baseline and 12 months in each group, and also looked for inter-group changes. In the omega-3 group, the median level of PAPP-A rose from 0.47 mU/l to 0.56 mU/l (p < 0.001). In the same group, sCD-40 L decreased from a mean baseline value of 5.19 ng/ml to 2.45 ng/ml (p < 0.001) and MMP-9 decreased nonsignificantly from 360.50 ng/ml to 308.00 ng/ml. Corresponding values for the corn oil group were 0.54 mU/l to 0.59 mU/l for PAPP-A (p = 0.007), 5.27 ng/ml to 2.84 ng/ml for sCD-40 L (p < 0.001) and 430.00 ng/ml to 324.00 ng/ml for MMP-9 (p = ns), respectively. In conclusion; both interventions resulted in a significant rise in PAPP-A, a significant decrease in sCD40L and a non-significant decrease in MMP-9 after 12 months of treatment in MI survivors. No inter-group differences were noted.

[PAPP-A in the first trimester of pregnancy]. / PAPP-A v prvním trimestru tehotenství.

OBJECTIVE: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. The aim of this study was to determine preliminary the medians of pregnancy-associated plasma protein A (PAPP-A) in the first trimester of pregnancy and to compare PAPP-A with other biochemical markers used for biochemical prenatal screening. DESIGN: Retrospective study. SETTING: First Institute of Medical Chemistry and Biochemistry and Institute for Clinical Biochemistry, First Medical Faculty, Charles University. Institute for Care of Mother and Child, Prague. PATIENTS: One hundred forty one pregnant women, who undergo biochemical prenatal screening for chromosomal disorders between 7th and 13th week were studied. In addition six women in the second trimester and five women with twin pregnancies, two cases of trisomy 21 and one case of trisomy 18 in second trimester were available for study. METHODS: Maternal serum levels of PAPP-A, human chorionic gonadotropin (hCG) and alfa-1-feto-protein (AFP) were measured using ELISA methods. A single radial immunodiffusion was used to determine trophoblast-specific-beta-1-glycoprotein (SP1). RESULTS: PAPP-A levels increased throughout the first trimester with median 1.8 mg/l in the 7th week to 23.0 mg/l in the 13th week of pregnancy. PAPP-A serum levels from 3 women with twin pregnancies were higher than in women with singleton pregnancies. Serum levels of PAPP A in two women with fetus affected by chromosomal disorders did not differ from normal pregnancies. Correlation coefficients between PAPP-A and AFP and between PAPP-A and SP1 were statistically significant (r = 0.42, P < 0.001, respectively r = 0.54, P < 0.001). The levels of PAPP-A and HCG did not correlate significantly (r = 0.019, P = 0.82). CONCLUSION: We established first trimester medians for PAPP-A, which are necessary for evaluation of the pathological values. We found statistically significant correlation between PAPP-A and SP1 and PAPP-A and AFP.

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

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