Reference Values of D-Dimers and Fibrinogen in the Course of Physiological Pregnancy: the Potential Impact of Selected Risk Factors—A Pilot Study

Pregnancy predisposes to thrombotic hemostasis, reflected in the laboratory as, e.g., increased levels of D-Dimers and fibrinogen, but in physiological pregnancy, the risk of venous thrombosis does not increase. Risk may increase if gestational diabetes mellitus (GDM) or nicotinism coexists. Study aims were to determine reference values for D-Dimers and fibrinogen concentrations in each trimester of pregnancy, corrected for GDM and nicotinism. Subjects and Methods. The study involved 71 pregnant women aged 25-44 y. Venous blood was collected three times: in the first (11-14 weeks), second (20-22 weeks), and third (30-31 weeks) trimesters. D-Dimer concentrations were determined by an enzyme-linked fluorescence assay, fibrinogen concentrations by a coagulation method according to Clauss. Results. Significant increases in D-Dimers and fibrinogen concentrations were observed, increasing with successive trimesters (p ANOVA<0.0001). Furthermore, a positive correlation between D-Dimers and fibrinogen was detected in the second trimester of pregnancy (r=0.475; p<0.0001). In addition, a significantly higher fibrinogen concentration was found in women with GDM compared to without GDM (p=0.0449). Reference ranges for D-Dimers were established, in trimester order, as follows: 167-721 ng/mL, 298-1653 ng/mL, and 483-2256 ng/mL. After adjusting for risk factors, significantly higher D-Dimer values (mainly second and third trimesters) were obtained: 165-638 ng/mL, 282-3474 ng/mL, and 483-4486 ng/mL, respectively. Reference ranges for fibrinogen were, in trimester order, 2.60-6.56 g/L, 3.40-8.53 g/L, and 3.63-9.14 g/L and, after adjustment for risk factors, 3.34-6.73 g/L, 3.40-8.84 g/L, and 3.12-9.91 g/L. Conclusions. We conclude that the increase in D-Dimers and fibrinogen levels in women with physiological pregnancy was compounded by gestational diabetes (GDM) and nicotinism. Therefore, D-Dimers and fibrinogen pregnancy reference values require correction for these risk factors.

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Value of Phenylalanine in Amniotic Fluid Detected by MS/MS for Screening of ma ternal PKU in the Second-Trimester

10.21203/rs.3.rs-42259/v1 ◽

2020 ◽

Author(s):

yanyun wang ◽

yun Sun ◽

yu-guo Wang ◽

tao Jiang

Keyword(s):

Amniotic Fluid ◽

Reference Values ◽

Venous Blood ◽

Dried Blood Spots ◽

Unknown Etiology ◽

Case Group ◽

Multiple Gestation ◽

Second Trimester ◽

Maternal Phenylketonuria ◽

Blood Spots

Abstract Background: Phenylketonuria is the most common inherited metabolism disease in China. This study aimed to identify a new, sensitive, simple, and easy method of screening maternal Phenylketonuria in the fetal stage.Methods: Samples of amniotic fluid, dried blood spots, and blood collected on the same day were obtained from women in the second-trimester (16–28 weeks). Women had to meet the following criteria: (i) isolated high risk of quadruple marker screening or cell-free DNA screening, (ii) women who gave birth to at least one child with intellectual disability of unknown etiology, and (iii) women who gave birth to a child who died young from unknown etiology. The exclusion criteria were as follows: clinically evident chorioamnionitis, multiple gestation, and laboratory signs of infection in the amniotic fluid sample. Phenylalanine levels were measured using tandem mass spectrometry. Women who met criterion (i) served as controls whose results were used to set reference values of Phenylalanine in amniotic fluid. Women who met criteria (ii) and (iii) served as the case group whose results were used to check for maternal Phenylketonuria. The Spearman rank correlation test was used to analyze the correlation of Phenylalanine in amniotic fluid and in venous blood. Results: We analyzed 365 samples of amniotic fluid. Among them, 345 were included in the control group, with reference values of Phenylalanine in amniotic fluid of 10.79–48.47 µmol/L. Twenty cases were included in the case group. One woman in the case group was diagnosed with hyperphenylalaninemia whose fetus was diagnosed with maternal Phenylketonuria by comprehensive analysis of Phenylalanine in dried blood spots and in amniotic fluid, head circumference in fetal ultrasound, and a previous history of adverse pregnancy. The correlation between Phenylalanine concentrations in venous blood and in amniotic fluid was weak.Conclusions: Phenylalanine can be readily measured in amniotic fluid. Relative to controls, amniotic fluid levels of Phenylalanine was increased in maternal Phenylketonuria. These results can support the use of Phenylalanine as a screening tool for maternal Phenylketonuria. The significance of these change requires further study.

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Early detection of patients at high risk for gestational diabetes in the early second trimester in patients with significant risk factors

American Journal of Obstetrics and Gynecology ◽

10.1016/s0002-9378(97)80696-5 ◽

1997 ◽

Vol 176 (1) ◽

pp. S179

Author(s):

S. Puza ◽

N. Roth ◽

M. Malee

Keyword(s):

Risk Factors ◽

High Risk ◽

Early Detection ◽

Gestational Diabetes ◽

Significant Risk ◽

Second Trimester

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Gestational diabetes mellitus prediction model: A risk factors analysis of pregnant women with gestational diabetes mellitus but have normal oral glucose tolerance test results in the second trimester of pregnancy

Technology and Health Care ◽

10.3233/thc-218006 ◽

2021 ◽

Vol 29 ◽

pp. 57-63

Author(s):

Jiayu Lu ◽

Song Zhang ◽

Hongqing Jiang ◽

Lin Yang ◽

Dongmei Hao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Second Trimester ◽

Oral Glucose Tolerance

BACKGROUND: Oral glucose tolerance test (OGTT) is a standard for the diagnosis of gestational diabetes mellitus (GDM). However, clinically, some cases with normal results were diagnosed as GDM in the third trimester. OBJECTIVE: To establish a risk model based on energy metabolism, epidemiology, and biochemistry that could predict the GDM pregnant women with normal OGTT results in the second trimester. METHODS: Qualitative and quantitative data were analyzed to find out the risk factors, and the binary logistic backward LR regression was used to establish the prediction model of each factor and comprehensive factor, respectively. RESULTS: The risk factors including the rest energy expenditure per kilogram of body weight, oxygen consumption per kilogram of body weight, if more than the weight gain criteria of the Institute of Medicine, the increase of body mass index between the second trimester and pre-pregnancy, and fasting blood glucose. By comparison, the comprehensive model had the best prediction performance, indicating that 85% of high-risk individuals were correctly classified. CONCLUSION: Energy metabolism, epidemiology, and biochemistry had better recognition ability for the GDM pregnant women with normal OGTT results in the second trimester. The addition of metabolic factors in the second trimester also improved the overall prediction performance.

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Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy

Bioscience Reports ◽

10.1042/bsr20202296 ◽

2020 ◽

Author(s):

Huijia Lin ◽

Mudan Ye ◽

Zhenwen Zhou ◽

Lianxiong Yuan ◽

Gendie Lash ◽

...

Keyword(s):

Risk Factors ◽

Thyroid Hormone ◽

Reference Values ◽

Early Pregnancy ◽

Maternal Age ◽

Thyroid Dysfunction ◽

First Trimester ◽

Reference Ranges ◽

Study Objective ◽

Maternal Parity

Objective: Thyroid dysfunction is a common endocrine problem during pregnancy, correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyroxine (FT3). Design, patients, measurements: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4 to 12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles. Results: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11-3.67 mIU/L; FT3, 3.19-5.91 pmol/L; FT4 10.95-16.79 pmol/L. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations. Conclusions: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23, maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.

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Early second trimester retinol-binding protein-4 values in cases with or without gestational diabetes mellitus risk factors: A cross-sectional study

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.12499 ◽

2014 ◽

Vol 41 (1) ◽

pp. 55-61 ◽

Cited By ~ 2

Author(s):

Asli Yarci Gursoy ◽

Gulsah Aynaoglu ◽

Gamze Sinem Caglar ◽

Feride Soylemez

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Gestational Diabetes ◽

Cross Sectional Study ◽

Retinol Binding Protein ◽

Second Trimester ◽

Sectional Study ◽

Cross Sectional ◽

Retinol Binding Protein 4 ◽

Diabetes Mellitus Risk

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Thrombin generation, D-dimer and protein S in uncomplicated pregnancy

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-1030 ◽

2015 ◽

Vol 53 (12) ◽

Cited By ~ 10

Author(s):

Mirjana K. Kovac ◽

Sanja Z. Lalic-Cosic ◽

Jelena M. Dmitrovic ◽

Valentina J. Djordjevic ◽

Dragica P. Radojkovic

Keyword(s):

Pregnant Women ◽

Reference Values ◽

Gestational Age ◽

Protein S ◽

First Trimester ◽

Second Trimester ◽

Third Trimester ◽

The Third ◽

D Dimer ◽

Protein S Activity

AbstractGestational age-specific reference values are essential for the accurate interpretation of haemostatic tests during pregnancy.Our 1-year prospective study included 40 healthy pregnant women with a median age of 30 (range 22–40) years; the subjects were followed in order to establish the gestational age dependent values for endogenous thrombin potential (ETP), D-dimer and protein S (activity and free).During the first trimester 50% of studied women had ETP >100% (reference values out of pregnancy); in the second trimester an ETP over 100% was observed in all women; ETP values remained unchanged during the third trimester. In the first trimester, the median D-dimer concentration of 0.30 mg/L, in the second 0.91 mg/L and in the third of 1.45 mg/L were observed. During the first trimester 14/40 subjects had protein S activity below reference range (<59%, out of pregnancy); the median value of 61.35; interquartile range (IQR) 20.38; in the second 21/37; the median value of 53.1 (IQR 15.65); in the third trimester 28/37 had low level of protein S activity with the median value of 49.0 (IQR 18.8). Free protein S showed a slight decrease from the first trimester; it remained almost stable during the rest of pregnancy, with the equal number of pregnant women with reduced free protein S.Related to the gestational age, a significant increase of ETP and D-dimer, from the second trimester was observed; the decrease of protein S was observed already from the early pregnancy, with more pronounced variability of protein S activity.

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