[Maternal biochemical screening -- an approach for genetic prevention. part 1. first and second trimester screening].

UNLABELLED: The aim is to perform our eight-year experience on prenatal (matemal) screening for Down syndrome (DS). METHODS: Pregnant women underwent screening in second trimester (ST2) - 14(+4)-19(+3) gestational week using serum AFP and free beta-hCG biochemical markers. A more sensitive first trimester test has been implemented in 11(+0)-13(+6) gestational weeks since the end of 2009. This combined screening test (CST1) was based on US measurements of NT (nuchal translucency) and NB (nasal bones) supplemented by biochemical markers of serum free beta-hCG and PAPP-A. Uniform methodology, web-based software and system for laboratory quality control had been used. False positive ratios for DS were estimated at cut-offs 1/250 for Down syndrome and 1/100 for Edwards syndrome. RESULTS: The test was performed on 17 468 pregnant women: 13 016 by biochemical screening 2 test (BHS2) and 4452 by first trimester test CST1. High risk for a chromosome disorder by BHS2 test was found in 1097 (8,4%) cases (5,96% < 35 years and 21,13% > 35 years). 7 fetuses were diagnosed with chromosome disease (5 fetuses with trisomy 21,1 - trisomy 18 and 1 - triploid); false positive were 1090 (8,4%). High risk for a chromosome disorder by CST1 test was found in 102 (2,3%) cases. 4 affected fetuses were diagnosed (3 with trisomy 21 and 1 with trisomy 13). Verified diagnosis for DS by first and second trimester tests were 43% (3 out of 7 cases) with 57% false negative results and 45,5% (6 out of 11 cases) with 54,5% false negative results respectively. Description of biochemical values/MoMs and US measurements are applied. CONCLUSIONS: We comment on the importance of US measurements in CST1 test and correct analysis of biochemical and US markers in counseling of every individual patient, beyond final risk number.

[Maternal biochemical screening -- an approach for genetic prevention. part 2. sequential approach with integrated risk assessment].

UNLABELLED: Performance of 2,5 year experience onprenatal (maternal) screening by integrated risk for Down syndrome and Edwards syndrome is presented in pregnant women underwent first (11(+0)-13(+6) g.w) and second trimester screening (14(+4)-19(+3) g.w), assessed by an integrated risk. Since the end of 2010 the most common strategy has been combination of both risks after contingent screening approach (serummarkers and US measurments from first test with indication to second trimester screening if the risk is intermediate or high and CVS diagnosis has been refused). Serummarkers were measured by fluorimetric immunoassay (Delfia) and risks were calculated using LifeCycle 3.2 software. RESULTS: The test was performed on 491 women, less than 4452 and 13 016 women first and second trimester respectively. We found highrisk for a chromosome disorder in 32 (6,5%) cases: 19 (6,35%) women < 35 and 13 (6,7%) women > 35). Diagnosis of a chromosome diseases was found in 4 fetuses out of 32 (12,5%): 3 fetuses with trisomy 21 and 1 with trisomy 18. False positive results were found in 28 out of 491 (5,7%) women. Verified diagnosis on lyfor DS was found in 3 out of 4 cases (75% sensitivity), and false negative results in 25%. Discussion is focused on the comparison of the screening approaches - the sensitivity, limitation sand the step wise sequential testing way with integrated risk of achieving a high performance of screening.

[The experience of the genetic laboratory in Varna on maternal serum screening for a six year period].

The aim of the presentation is to report the results of the Genetic laboratory in University hospital "St. Marina" Varna on second (15-19 gw) and first trimester (12-14 gw) maternal serum screening for common chromosome disorders, for the period 2005-2010. The test was performed on 10741 pregnant women from 8 regions of North-Eastern Bulgaria: 9743 women were screened in the second trimester (8251 at the age < 36 and 1492 at the age > 36) and 998 women - in the first trimester (827 at the age < 36 and 171 at the age > 36). The fluorimetric dual method was based on biochemical markers; software calculated risk as function of precise gestational age, maternal weight and age. The most common strategy was to combine the risk as determined from first and second trimester screening test in a sequential manner. High risk for a chromosome disorder (a risk above 1:250) was found by second trimester screening in 784 (8,04%): 488 (5,91%) <36 and 296 (19,83%) >36. The most recent first trimester screen test, which have been involved in the laboratory since April 2010 detected 7 (0,84%) and 23 (13,45%) women respectively to the age groups with increased risk for a chromosome disease. Additional ultrasonographic scan confirmed the biochemical risk for a serious Neural Tube/Abdomainal Wall defects in 5 out of 32 fetuses with increased risk for these defects; other 3 fetuses were detected to be involuntary miscarried as "missed abortion", 1 triploidy included. We comment on the sensitivity, limitations and the stepwise sequential testing way of achieving a high performance of screening for chromosome diseases based on preliminary information to pregnant women on different options for a contemporary approach for genetic prevention.

[Impact of inherited thrombophilia on the development of some pregnancy complications].

AIM: To assess the clinical significance of inherited thrombophilia [IT] for the development of some pregnancy complications. MATERIAL AND METHODS: The incidence of the following factors was studied in 97 pregnant women with pregnancy complications and in 103 controls: R506Q mutation encoding Factor V Leiden [FVL] synthesis, Prothrombin G20210A mutation, T677 methylenetetrahydropholate reductase mutation [MTHFR], 4G/4G polymorphism of the plasminogen activator inhibitor [PAI 4G/4G]. Among 97 patients in the group studied 39 had early onset severe preeclampsia [PE], 14--placental abruption [AP] without PE, 18--intrauterine growth restriction [IUGR] without PE, 12--stillbirth [SB] without PE, 14--habitual spontaneous abortions [HSA]. The control group included 103 clinically healthy pregnant women with at least one previous uneventful pregnancy, without history of thromboembolic disorders. In addition, patients with severe PE with and without IT were compared regarding g. a. and birthweight at delivery and intrauterine fetal loss rate. DNA analysis was performed according to internationally accepted standards. Pregnancy outcomes were ascertained from hospital records. Statistical significance (p < 0.05) was assessed by means of Student's t-test. RESULTS: FVL mutation was found in 23.7% (23/97) of the patients from the studied group and in 5.8% (6/103) of the controls. Prothrombin G20210A carriers were 11% (11/97) of the studied and 3.8% (4/103) of the controls, while with PAI 4G/4G polymorphism they were 30.9% (30/97) and 14.5% (15/103) respectively. MTHFR T677 was not more frequent in the studied group (8.2%) compared to the control one (29%). Eight of the patients (9.6%) were carriers of more than one mutation. In 22 cases with early onset severe PE and IT gestational age and birthweight at delivery were lower than in the cases with severe PE without IT while intrauterine fetal loss rate did not differ significantly between the two groups. CONCLUSIONS: Inherited thrombophilia is found more frequently in women with pregnancy complications like PE, IUGR, AP, SB, HSA. The incidence of homozygous MTHFR T677 is not higher in these cases. IT worsens the prognosis of severe PE. The diagnosis of IT is important since anithrombotic therapy has to be considered to protect the mother and the fetus.

[Attitude of pregnant women towards prenatal screening for chromosomal and structural fetal anomalies between 11-14 weeks of gestation].

AIM: The aim of the present survey is to analyze the attitude of pregnant women towards the possibilities of prenatal screening and diagnosis between 11-14 weeks of gestation (w.g.). MATERIAL AND METHODS: Overall 109 pregnant women, hospitalized in SBALAG "Maichin dom", received written information about the possibilities for prenatal screening and diagnosis between 11-14 w.g. and 16-20 w.g., as well as a comprehensive description of the potential advantages and disadvantages of the different approaches/methods of screening/diagnosis. Consequently, the patients were asked to answer 13 closed and semi-closed questions in an anonymous enquiry. RESULTS: Overall 97,2% (106/109) of the women agreed to perform an ultrasound examination for fetal nuchal translucency measurement as a screening tool for chromosomal anomalies between 11-14 w.g. Furthermore, 82,6% (90/109) preferred the option of first trimester biochemical screening, rather than screening in the second trimester. On the other hand only 62,4% (68/109) accepted chorionic villous sampling between 11-14 w.g. in comparison to 83,5% (91/109) who agreed to perform an amniocentesis between 16-20 w.g. CONCLUSION: The vast majority of women prefer prenatal screening programs to be scheduled in the first, rather than in the second trimester. However, most women would still choose for a relatively safer second trimester invasive procedure instead of the option of earlier prenatal diagnosis.

[Second trimester Down syndrome serum screening--results from a pilot study]. / Serumen skrining za sindrom na Daun vuv vtori trimestur na bremennostta--rezultati ot pilotno prouchvane.

The results from a pilot prospective study--second trimester Down syndrome [DS] serum screening between 15 and 21 w.g. with two markers (alpha-fetoprotein and free bb-hCG)--were summarised. Sensitivity, false-positive rate [FPR], positive predictive value [PPV] of the screen positive and negative predictive value [NPV] of the screen negative result for the sbgroups II and below 35 years of age were analysed. The uptake for invasive prenatal testing in screen positive patients and the percentage of terminated pregnancies with prenatally diagnosed DS fetuses as well as the ratio "lost unaffected pregnancies/1 DS fetus diagnosed antenatally" were also calculated. High sensitivity of the DS serum screening was achieved--75% and 87.5% in the subgroups below and II the age of 35 respectively with 6.6 and 31.7% FPR. With higher DS age risk the PPV of the screen positive test was higher and the NPV of the screen negative result--lower. The percentage of invasive prenatal testing in screen positive patients was high (average 83.4%) without significant differences in the two age subgroups. Pregnancy was terminated in all cases with antenatally diagnosed DS fetuses. The ratio "lost unaffected pregnancies/1 DS fetus diagnosed antenatally" for serum screening was lower compared to the same ratio when screening by age. The results from our pilot study (serum screening sensitivity and FPR, uptake for invasive testing in screen-positive cases) are comparable to the ones reported in literature. This is an important prerequisite for introduction of mass DS screening for our population.

[Pregnancy complications with abnormal results of biochemical screening for Down syndrome in second trimester and normal fetal karyotype]. / Uslozhneniia na bremennostta pri abnormni rezultati ot biokhimichnite skriningovi testove za sindrom na Daun vuv vtori trimectur i normalen kariotip na ploda.

Pregnancy complications were studied in the following groups of pregnancies with structurally and chromosomally normal fetuses: 1) 216--with elevated free beta-hCG above 2 MoM and 134--above 2.5 MoM; 2) 37--with elevated alpha-fetoprotein [AFP] above 2 MoM; 3) 67 screen-positive patients below the age of 35. The following complications were compared in the studied and the control groups: preterm delivery and premature rupture of membranes [PROM], preeclampsia (in general and severe one), IUGR without preeclampsia, delivery of small for gestational age [SGA] and low birth weight [LBW] infants and perinatal fetal loss. Pregnancy outcome in cases with free beta-hCG above 2 MoM was not different from that in the control group. With 2.5 cut-off level the incidence of preeclampsia and of LBW infants was higher in the studied than in the control group. Elevated AFP above 2 MoM alone was associated with more frequent preeclampsia including severe one (in all the latter cases--IUGR present). In the screen-positive group the incidence of preeclampsia (in general and severe one with IUGR), SGA and LBW infants and perinatal mortality rate were significantly higher than in the control group. No difference was found between the studied and the control groups regarding subsequent development of IUGR without preeclampsia, preterm delivery and PROM. Abnormal second trimester serum screening test results (elevated free beta-hCG or AFP alone above 2.5 and 2 MoM respectively) in pregnancies with normal fetal karyotype indicate higher risk for subsequent development of preeclampsia. Screen-positive patients, being a heterogeneous group (including ones with elevated free bb-hCG alone and ones with elevated both free beta-hCG and AFP), are at increased risk for other pregnancy complications too.

[The plasma amino acid profile of women with a normal pregnancy and in pre-eclampsia]. / Plazmen amino-kiselinen profil na zheni s normalna bremennost i s preeklampsiia.

The authors studied the level of some amino acids in the plasma of 10 women with normal pregnancy as well as of 16 women with moderate form of pre-eclampsia. 21 amino acids were determined by a liquid chromatograph, consisting of an automatic controller of the gradient, nonautomatic injector, fluorimetric detector and recording device. The results showed that there were differences in amino-amides of women with normal pregnancy and of nonpregnant women. Concentrations of a large part of amino acids were not changed, but some of them increased--aspargic acid, glutamate, threonine and phenylalanine or reduced--cytroline, methionine, ornithine, glycine, aspargine, alpha-amino acid during pregnancy. The values of amino-acids in women with normal pregnancy and in women with moderate form of preeclampsia did not differ. Ethanol-amine is the only exception and it is found in almost half of the women with preeclampsia. This is an original finding, which deserves further study.

[Dynamics of lysosomal enzymes in patients with allergic dermatoses before and after high altitude climate therapy]. / Dynamik lysosomaler Enzyme bei Patienten mit Allergodermatosen vor und nach Hochgebirgsklimatherapie.

Lysosome enzymes were measured in patients with allergic dermatosis before and after high altitude climate therapy. The activity of five acid lysosomal hydrolases in the serum of patients with allergic dermatoses before and after 30 days were investigated. In all cases a reduction of the activity of alpha-glucosidase was observed. A similar reduction of the activity of beta-glucuronidase and beta-galactosidase was observed.