Association between uterine leiomyomas and the biochemical screening test results in the first and second trimester of pregnancy: a pilot study.

OBJECTIVES: The presence of the uterine leiomyomas may change the concentrations of the screening serum markers and so after the risk calculation of the fetal chromosomal abnormalities. PURPOSE: To estimate the influence of the uterine leiomyomas on the first and second trimester serum markers concentrations. MATERIAL AND METHODS: The studied group consisted of 127 women between 11 and 20 weeks of normal singleton pregnancy. In each patient, the uterine leiomyomas were diagnosed - over 20 mm in the diameter and located in the uterine wall. Seventy-seven patients had undergone the first trimester screening, 50 patients the second trimester screening. The control group consisted of 1020 women between 11 and 20 weeks of normal singleton pregnancy without uterine leiomyomas. RESULTS: In the first trimester group, the pregnancy-associated plasma protein A serum concentrations were not different from the controls. The median concentrations of free beta-human chorionic gonadotrophin (ß-hCG) were significantly higher (1.43 MoM). In the second trimester group, no significant differences in AFP and estriol median concentrations were observed, while the median value for free ß-hCG was significantly higher (2.01 MoM) than in control group. CONCLUSIONS: The presence of the uterine leiomyomas may increase maternal serum concentration of the ß-hCG and so after the rate of the false positive results of the prenatal screening tests.

[Biochemical prenatal tests and uterine artery Doppler examination in prediction of PIH and IUGR in the third trimester of pregnancy]. / Biochemiczne testy prenatalne i badanie dopplerowskie tetnic macicznych w predykcji PIH i IUGR w III trymestrze ciazy.

OBJECTIVES: PIH and IUGR are serious complications in the third trimester of pregnancy. Many publications claim a connection between false positive prenatal tests and subsequent occurrence of PIH and IUGR. DESIGN: The aim of the study was to estimate the usefulness of the biochemical markers of fetal defects and uterine Doppler examination in predicting PIH and IUGR in the third trimester of pregnancy. METHODS: We examined 156 pregnant patients in The Department of the Fetal Medicine and Gynecology Medical University of Lodz, between 2006-2009. In case of each pregnant woman we estimated biochemical markers in the first (PAPP-A + beta-hCG) and second trimester (AFP, beta-hCG, uE3 - triple test). Each patient underwent three ultrasonographic examinations in the first, second and third trimester (between 11-13, 15-20, and 22-27 weeks gestation, respectively) with uterine artery Doppler examination. We monitored these pregnancies for PIH and IUGR and divided them into three groups: 28 patients with PIH (study group 1), 14 patients with IUGR (study group 2), and 114 patients with uncomplicated pregnancies (controls). RESULTS: In both study groups we observed: higher concentration of beta-hCG, higher percentage of the positive biochemical prenatal tests and abnormal uterine artery Doppler waveform. Positive triple test was the strongest predictor of PIH and IUGR (PPV=60.87% for PIH and PPV = 30.77% for IUGR). CONCLUSIONS: Biochemical markers and abnormal uterine artery Doppler waveform are associated with PIH and IUGR. These parameters can be the base for the test identifying pregnant patients with high risk of PIH and IUGR.

[The role of fetal nuchal translucency (NT) and ductus venosus blood flow (DV) in the detection of congenital heart defects]. / Ocena przeziernosci karkowej (NT) oraz spektrum przeplywu w przewodzie zylnym (DV) w wykrywaniu wad serca plodu.

UNLABELLED: Cardiac defects, the most common forms of congenital defects, are found in 3-8 of every 1000 pregnancies. Currently only 15-30% of CHD in newborns is detected prenatally. There are different strategies to increase the prenatal detection of cardiac abnormalities. Nuchal translucency screening and ductus venosus blood flow have been suggested to be useful methods of identifying cardiac anomalies in chromosomally normal fetuses. OBJECTIVE: To examine the association between nuchal translucency thickness and ductus venosus blood flow between 11-13.6 week of pregnancy and CHD in chromosomally normal fetuses. MATERIAL AND METHODS: Patients with singleton pregnancies at 11 to 13.6 weeks of gestation were recruited to undergo nuchal translucency sonography. The prevalence of major cardiac defects was determined and the utility of screening for nuchal translucency thickness including sensitivity, specificity, and positive and negative predictive values, were calculated for the NT thickness cut off points of the 95th and 99th centile for CRL. Ductus venosus Doppler ultrasound blood flow velocity waveforms were obtained at 10-13.6 weeks gestation. RESULTS: 4720 gestations were analyzed, of which 13 newborn infants had CHD. The incidence of major CHD increased with increasing NT. Sensitivity specificity and positive predictive values were 45.4%, 92% and 1.5% at 99.8th percentile, and 25%, 98.5%, 3.2% and 99.8% at 99th percentile. Reverse or absent flow during atrial contraction was observed in 8 out of the 13 (61.5%) chromosomally normal fetuses with CHD. CONCLUSION: Measurement of fetal nuchal translucency thickness and ductus venosus blood flow at 11-13.6 weeks of pregnancy is a sensitive method of screening for CHD. The prevalence of CHD increases with increasing fetal NT and abnormal ductus venosus blood flow. Increased NT or abnormal ductus venosus blood flow is a strong indication for fetal echocardiography.

[Interpretation of false positive results of biochemical prenatal tests]. / Interpretacja falszywie dodatnich wyników biochemlcznych testów prenatalnych.

Modern, non-invasive prenatal diagnostics based on biochemical and ultrasonographic markers of fetal defects allows us to calculate the risk of fetal chromosomal aneuploidies with high sensitivity and specificity An introduction of biochemical, non-invasive prenatal tests turned out to result in frequent false positive results of these tests in cases when invasive diagnostics does not confirm fetal defects. However prospective analysis of these cases showed numerous complications in the third trimester of the pregnancies.

[Noninvasive prenatal test in the first trimester of pregnancy (NT and estimation of beta-hCG and PAPP-A) in the diagnosis of fetal abnormalities in Polish population--comparison of the biochemistry own normal ranges and literature reported data]. / Nieinwazyjny test prenatalny w I trymestrze ciazy (pomiar NT oraz oznaczenia beta-hCG i PAPP-A) w diagnostyce wad plodu w populacji polskiej--porównanie biochemicznych norm wlasnych i danych swiatowych.

THE AIM OF STUDY: Estimation of Polish population standards of the concentrations of pregnancy-associated plasma protein--A (PAPP-A) and free beta--human chorionic gonadotropin (beta-HCG) in the maternal blood between 10.0 and 13.6 week of pregnancy and comparison of the biochemistry own normal ranges and literature reported data. Estimation the sensitivity of the fetal nuchal translucency measurement, biochemical concentrations of PAPP-A and free beta-HCG in detection of the fetal chromosomal abnormalities. MATERIAL AND METHODS: 582 women in the age 14 to 46 years old with singleton pregnancies were included to the study The screening was performed between 10.0 and 13.6 week of gestation. The fetal nuchal translucency serum concentrations of PAPP-A and free beta-HCG were measured. The specific risk was calculated using the Fetal Medicine Foundation software (FTS) by accredited sonographers. RESULTS: Standards for serum concentrations of PAPP-A and free beta-HCG in normal pregnancies were determined. The measurement sensitivity of the fetal nuchal translucency in detection of the fetal chromosomal abnormalities was 80% and sensitivity of serum concentrations of PAPP-A and free beta-HCG was 40% and 80%. CONCLUSIONS: There is no significant differences between estimated biochemistry standards (PAPP-A and free beta-HCG) for Polish population and literature reported data. Observed differences in measurements of fetal NT, serum concentrations of PAPP-A and free beta-HCG in a control group and the group with the aneuploidies confirmed usefulness of these methods for the first trimester prenatal screening.

[Connection between uterine myomas and biochemical screening results in the first and second trimester of pregnancy]. / Ocena wplywu obecnosci miesniaków macicy na stezenia markerów biochemicznych testów przesiewowych w I i II trymestrze ciazy.

OBJECTIVES: Uterine myomas may change the concentrations of the screening serum markers and therefore alter the risk calculation of the fetal chromosomal abnormalities. An increased risk leads to invasive diagnostics procedures which in these cases can often be technically difficult due to the presence of myomas. AIM: The aim of this study was to assess the influence of uterine myomas on the first and second trimester serum markers concentrations and, possibly on the test results. MATERIAL AND METHODS: The study group consisted of 127 women between 11 and 20 weeks of normal singleton pregnancy. In each case uterine myomas were diagnosed--over 20 mm in the diameter and located in the uterine wall. 77 patients underwent the first trimester screening (PAPP-A & free beta-hCG) and 50 patients had the second trimester screening (triple test). The control group consisted of 1020 women between 11 and 20 weeks of normal singleton pregnancy without uterine myomas. Delfia Xpress analyser was used for the serum markers estimations. All pregnant women delivered normal healthy babies. RESULTS: In the first trimester group the PAPP-A serum concentrations were not different from the controls while the mean median concentration of free beta-hCG were significant higher--1.43 MoM. In the second trimester group the following mean median values were observed: no significance for the AFP--1.18 MoM and estriol--1.29 MoM and significantly higher mean median value for the free beta-hCG--2.01 MoM. CONCLUSIONS: 1. The presence of the uterine myomas is connected with the increased maternal serum concentration of the beta-hCG, particularly in the second trimester. 2. The uterine myomas may lead to the increased rate of the false positive results of the prenatal screening test, especially the triple test.

[Thrombotic thrombocytopenic purpura in pregnancy. A case report]. / Zakrzepowa plamica maloplytkowa w ciazy--opis przypadku.

Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. About 10-20% of TTP cases are associated with the pregnancy. Preterm delivery and intrauterine fetal death are frequent pregnancy complications of TTP. The following paper presents the case of a 32-year-old woman with TTP relapse at 10 weeks of her second pregnancy. Despite regular fresh frozen plasma transfusions, intrauterine fetal death occurred at 21 weeks of gestation. Current views on TTP management during pregnancy have been presented in the article as well.

[Nasal bone (NB) length measurement in the first trimester of pregnancy in Polish population and its validity as fetal aneuploidy indicator]. / Nomogram dlugosci kosci nosowej (NB) w I polowie ciaiy w populacji polskiej oraz jego przydatnosc jako markera aneuploidii.

OBJECTIVES: Dynamic development of prenatal diagnostics is mostly directed towards search for non-invasive screening. The main role of the screening methods is to select high-risk fetal aneuploidy group of pregnant women. The base for the prenatal screening in modern obstetrics is ultrasound scanning. DESIGN: The aim of the study was to estimate typical value range for the fetal nasal bone length measurement (NB) between 11th and 20th week of pregnancy, in Polish population. The second aim was to assess the value of the parameter as an aneuploidy marker. MATERIALS AND METHODS: The study was conducted between 1999-2006, in the 1st Division of Obstetrics and Gynaecology, Medical University in lódz. The investigated population comprised 2960 pregnant women. 53 cases of the fetal chromosomal aneuploidies were diagnosed. RESULTS: Typical values for the nasal bone measurement were estimated. The investigations showed that until 13th gestation week, visualization of the presence or absence of the nasal bone on the ultrasound scan is a better marker for fetal aneuploidy diagnosis than the measurement. However, since the 14th week, it is the measurement that becomes the most adequate method of the fetal nasal bone assessment. CONCLUSIONS: (1) We estimated the normal value range for the fetal nasal bone length measurement (NB) between 11 and 20 weeks of pregnancy. (2) The nasal bone length is an useful marker for the fetal aneuploidy. 3. The predictive value of the method suggests the visualization of the nasal bone presence in the 1st trimester of the pregnancy as a screening method. The measurement of the NB proves to be a useful method in the prenatal diagnostic in the 2nd trimester of the pregnancy.

[Abnormal second trimester screening for fetal chromosomal abnormalities as a predictor of adverse pregnancy outcome]. / Nieprawidlowe stezenia markerów biochemicznych w II trymestrze a powiklania w dalszym przebiegu ciazy.

UNLABELLED: Second-trimester maternal serum markers (triple test) is common used to estimate of the fetal risk of genetic abnormalities and open neural tube defects. Positive results of the triple test concomitant with the normal fetus karyotype pattern can also predict the adverse pregnancy outcome. Many authors have been indicated such false positive results of the triple test in the cases of the uterine myomas, PIH, IUGR, and IUD. OBJECTIVE: The purpose of this study was to determine the association between abnormal second trimester Down syndrome screening markers and adverse pregnancy outcome. MATERIAL AND METHODS: A total of 775 pregnant women underwent maternal serum screening. Pregnancy complications were studied in the groups of pregnancies with structurally and chromosomally normal fetuses--with: elevated AFP > 1,89MoM, elevated beta-hCG > 1,69MoM or low beta-hCG < 0,48MoM. RESULTS: Increased maternal serum AFP > 1,89MoM were found to be significantly associated with IUGR, PIH and placental pathology. Increased beta-hCG > 1,69MoM were significantly associated with PIH and IUGR. Finally decreased beta-hCG < 0,48MoM were found to be significantly associated with IUGR, PIH and IUD. CONCLUSION: Triple test can be used not only for the detection of fetal chromosomal and NTD abnormalities but also for the detection of high-risk pregnancies.

Ultrasound diagnostic schema for the determination of increased risk for chromosomal fetal aneuploidies in the first half of pregnancy.

The aim of the study was to develop an early ultrasound diagnostic schema for the determination of increased risk for fetal chromosomal aneuploidies. The study was conducted on a population of 1318 pregnant women divided into 2 groups: 1255 women with the normal course of pregnancy and 63 women with diagnosed fetal abnormalities. There were 34 cases of chromosomal abnormalities (trisomy 21, 18, 13; triploidy; unbalanced inversion 9; deletion 16) and 29 cases of structural malformations. The estimation of the range of normal values was performed for the nuchal translucency (NT) measurement between 11 and 13 weeks and the nasal bone length (NB) measurement between 12 and 20 week. The results obtained in the collective set of normal pregnancies constituted the basis for the calculation of the range of normal values. The measurements of NB and NT showed a linear value increase with the pregnancy course. The following test characteristics (correlation to CRL) were recorded: NB - sensitivity 60%, specificity 98%, positive predictive value (PPV+) 43%, negative predictive value (NPV-) 98.9%. For the assumption that the test outcome means the presence or absence of the nasal bone in the ultrasound scan the sensitivity was 40%, but specificity 100%; NT - sensitivity 63.6%, specificity 98.2%, PPV+ 38.9%, NPV - 98.2%; NT + NB - presents similar characteristic to the NB or NT alone - sensitivity 55.6%, specificity 98.6%, PPV+ 50%, NPV - 98.9%. The following test characteristics for chromosomal aberration markers (correlation to BPD) were observed: NB - sensitivity 68.4%, specificity 97.4%, PPV+ 56.5%, NPV - 98.4%; NT - sensitivity 73.9%, specificity 97.9%, PPV+ 54.8%, NPV- 99.2%; NT + NB - sensitivity 94.7%, specificity 98.9%, PPV+ 90%, NPV - 99.7%, respectively. The "genetic sonogram" protocol for the structural defect detection was analysed: sensitivity was 80%, specificity 100%, PPV+ 100%, NPV - 99.7%. It is concluded that the new biometric parameter--nasal bone length (NB) and the corrected one--nuchal translucency thickness (NT) are useful markers for fetal abnormalities, especially for chromosomal aberrations. High predictive values of the diagnostic schema for the detection of aneuploidies and structural defects indicate that its application in correlation with the biparietal diameter (BPD) is highly recommended. The proposed schema is an effective algorithm for prenatal diagnostics characterised by high prognostic values. The possible introduction of the schema could result in a decrease of the invasive procedure rates, which could minimise the rate of miscarriages as a complication of amniocenteses.

[Estimation of ultrasonographic markers of chromosomal abnormalities in verification of second trimester maternal serum biochemistry]. / Ocena markerów ultrasonograficznych wad plodu w weryfikacji dodatnich wyników testu potrójnego.

UNLABELLED: In the case of positive triple test results the presence or absence of sonographic markers is associated not only with fetal abnormalities, but also with a variety of adverse outcomes of pregnancy. OBJECTIVE: Evaluation of sonographic markers of chromosomal abnormalities in verification of positive results of triple tests. MATERIAL AND METHODS: In consecutive series of 780 pregnant women we performed triple tests at 14-19 weeks. We reviewed the presence or absence of sonographic markers for fetal abnormalities including nuchal thickening (NT), nasal bones (NB), extermities (HL, FL), umbilical cord diameter (UCD), bowel echogenity (BE), renal pyelectasis (DPR) and chorioid plexus cyst (CPC). RESULTS: There were 47 (6.02%) positive results of triple tests including 36 (4.6%) cases with false positive result. In the group of affected fetuses we observed at least two sonographic markers. In the group with false-positive results 15 (41.6%) fetuses had adverse pregnancy outcome with only one ultrasound marker. CONCLUSION: Positive result of the triple test and the presence of two or more markers of fetal abnormalities increase the risk of fetal abnormalities, whereas absence or presence of only one marker and normal karyotype should classify pregnancy to high risk of adverse perinatal outcome.

[Factors involved in ketoacidosis at the onset of type 1 diabetes in childhood]. / Czynniki warunkujace wystapienie kwasicy ketonowej w momencie klinicznego rozpoznania cukrzycy typu 1 u dzieci.

BACKGROUND: In some patients the ketoacidosis at the onset of type 1 diabetes has been observed. AIM: The aim of this study was to investigate an effect of the clinical, genetic, immunological and metabolic parameters on the occurrence of ketoacidosis at the clinical onset of the disease. MATERIAL AND METHODS: 106 children with type 1 diabetes, aged 1.8-18.2 years (average 10.6), 40 female and 66 male, were studied. Diabetic ketoacidosis was defined as blood pH of less than 7.35 and severe acidosis as less than 7.2. Among the clinical features, age at onset of the disease and gender of patients were evaluated. Moreover, fasting C-peptide level, insulin requirement, HbA1c level, blood glucose level and body mass index normalized by age and sex were examined at the onset and 6, 12, 24 and 36 months after diagnosis. The HLA-DQA1 and DQB1 alleles and -23 HphI INS polymorphism and CTLA4 gene +49 polymorphism (PCR-RFLP) were studied and islet cell antibodies (ICA) as well as antibodies to glutamic acid decarboxylase (GADA) and thyrosine phosphatase antibodies (IA2A) were also determined. RESULTS: The presence of diabetic ketoacidosis was observed in 55% and severe form in 9% of children. In the group of patients with ketoacidosis lower C-peptide level and lower c-peptide/glycaemia ratio than in children without ketoacidosis were observed (0.20+/-0.18 vs. 0.31+/-0.28 pmol/ml and 0.07+/-0.05 vs. 0.20+/-0.17, p<0.003, respectively). The patients with fasting C-peptide at the onset below normal range (<0.28 pmol/ml) were at high risk of ketoacidosis, OR (95%CI)=3.3 (1.3-8.2). The patients with ketoacidosis were characterized by higher exogenous insulin requirement than non-ketoacidosis individuals (1.2+/-0.6 vs. 0.8+/-0.5 j/kg/24h, p=0.004). Besides, in patients with severe ketoacidosis higher level of IA2A was found as compared to other patients (73.4+/-44.9 vs. 44.2+/-39.6; p=0.04). In this group more frequently 2 and/or 3 different autoantibodies were observed (90% vs. 79%), although, the difference was not significant. CONCLUSIONS: The presence of diabetic ketoacidosis at clinical diagnosis of type 1 diabetes may be related to the residual b cell function, which is mainly determined by the intensity of immunological destruction.

[Severe hypoglycemia and insulin antibodies levels in children and adolescents with type 1 diabetes]. / Ciezkie hipoglikemie a poziom przeciwcial przeciwinsulinowych u dzieci i mlodziezy chorych na cukrzyce typu 1.

UNLABELLED: Severe hypoglycemia may limit the effects of type 1 diabetes treatment. Insulin antibodies were mentioned to be included in the pathogenesis of hypoglycemia in adult diabetic patients, particularly those treated with non-human insulins. The influence of insulin antibodies on the occurrence of hypoglycemia in children treated with human insulin was not studied. THE AIM of the study was to examine insulin antibodies titers in young type 1 diabetics with a recent history of severe hypoglycemia and in matched control subjects. MATERIALS AND METHODS: Insulin antibodies (IA) were assessed in 33 type 1 diabetic children (mean age 13.2, quartile interval 10.3-16.4) within 14 days after an episode of severe hypoglycemia. In 30 patients from this group, whose serum samples were collected also in the last two years preceding the episode of severe hypoglycemia and stored for routine immunologic assessment, IA levels before severe hypoglycemia were assessed, too. The control group consisted of 30 type 1 diabetic patients (mean age 14.4, quartile interval 12.7-15.4), who never experienced any severe hypoglycemia episode, and matched the study group for sex, age and diabetes duration. All patients were treated either with human insulin or with human insulin analogue lispro and NPH human insulin. Insulin antibodies were determined semi-quantitatively (as serum capacity to bind 125I-insulin) by radioimmunoassay. RESULTS: Compared to controls (median value 19.5%, quartile interval 13.7-30.1%), patients who experienced severe hypoglycemia had higher IA levels after (mean value 30.6%, quartile interval 16.8-39.1%, p<0.04) as well as before hypoglycemia (mean value: 35.9, quartile interval 21.6-46.8%, p<0.02). There was a strong correlation between IA levels measured before and after severe hypoglycemia episodes (r=0.7, p<0.0001) in the study group. CONCLUSIONS: High insulin antibodies levels may be markers of increased risk for severe hypoglycemia acting in a mechanism other than a simple imbalance between exogenous insulin, carbohydrate consumption and physical exercise.

[Alleles of HLA-DQB1 and familial aggregation of type 1 diabetes]. / Allele genu HLA-DQB1 a rodzinne wystepowanie cukrzycy typu 1.

The HLA complex, located on the short arm of chromosome 6, is the strongest genetic marker for type 1 diabetes (T1DM). In previous study we demonstrated association between genes HLA-DRB1 and HLA-DQB1 and T1DM in the Polish population. There is a strong-independent association of alleles HLA-DRB1*0401 and DQB1*302, despite population linkage disequilibrium among alleles of these genes. The aim of the current study was to verify a hypothesis that some alleles or haplotypes of HLA-DRB1, DQA1 and DQB1 genes increase the risk for familiar aggregation of T1DM. We analysed 507 patients with IDDM derived from 80 multiplex and 325 patients from simplex families. PCR and hybridisation with SSO probes performed HLA typing for DRB1, DQA1 and DQB1 alleles. Genetic analysis demonstrated strong association of allele HLA-DQB1*0302 with T1DM in the Polish population in families with single (DM1) and more numerous cases (DM2) cases, compared with healthy cases (n=103). The HLA-DQB1*302 allele frequencies were 27.8% vs 8.7%; Pc<10(-5); OR(95%CI)=4,03(3.80-4.25) and 16.3% vs 8.7%; Pc<0.04; OR(95%CI)=2.04(1.79-2.89), respectively. The presence of allele HLA-DQB1*0602 has a strong protective effect from T1DM in both studied groups (1.46% vs. 13.6%; Pc<10(-5); OR(95%CI)=0.09(-0.25-0.44) and 0.98% vs. 13.6%; Pc<10(-5); OR(95%CI)=0.06(-0.46-0.58), respectively. Interestingly, HLA-DRB1*04 allele more often co-segregated with DM2 families as comparing the DM1 group (31.0% vs. 15.8%, respectively; Pc<10(-5)). However in both cases differences remain significant as compared to controls: Pc<10(-5), OR (95%CI)=3.52(3.33-3.70) and Pc<10(-5) OR(95%CI)=6.17(5.97-6.37), for DM1 and DM2 respectively. Subtyping of HLA-DRB1*04 alleles demonstrated that the strongest predisposing effect has been identified with DRB1*0401. Moreover, difference in frequencies of the protective allele HLA-DQB1*0301 among DM1 and DM2 group was revealed (8.8% vs. 13.7%, respectively; Pc<10(-5)) and the protective effect of this allele remained only significant in DM1 group: 8.8% vs. 19.9%; Pc<10(-5); OR(95%CI)=0.39(0.19-0.58). The results suggest that it is likely that familial aggregation of T1DM is associated with lower frequency of protective alleles of HLA-DQB1 gene.