Evaluation of sFlt-1 and PlGF for predicting preeclampsia in pregnant women with diabetes mellitus

2021 ◽  
Vol 70 (4) ◽  
pp. 43-56
Author(s):  
Roman V. Kapustin ◽  
Elizaveta M. Tcybuk ◽  
Sergey V. Chepanov ◽  
Elena N. Alekseenkova ◽  
Ekaterina V. Kopteeva ◽  
...  

AIM: The aim of this study was to evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels in the blood of women with various types of diabetes mellitus, depending on the correction method applied, and to determine the prognostic significance of the sFlt-1 / PlGF ratio for predicting the development of preeclampsia in this patient population. MATERIALS AND METHODS: We examined 140 pregnant women who were included in six main study groups: type 1 diabetes mellitus (with or without pregravid preparation), type 2 diabetes mellitus (diet therapy or insulin therapy), and gestational diabetes mellitus (diet therapy or insulin therapy). The comparison groups consisted of pregnant women with preeclampsia and patients without complications of pregnancy. Using electrochemiluminescence analysis, PlGF and sFlt-1 levels in the blood serum were determined twice, at 11+013+6 and 30+033+6 weeks of gestation. Statistical data processing was performed using the IBM SPSS Statistics version 23 and GraphPad Prism version 8.0 software packages. RESULTS: In the blood serum of pregnant women with diabetes mellitus in the first and third trimesters of pregnancy, we found an increase in sFlt-1 level and a decrease in PlGF level, as well as an increase in the sFlt-1 / PlGF ratio. These changes were most pronounced in individuals with type 1 diabetes mellitus without pregravid preparation and with type 2 diabetes mellitus on insulin therapy. In patients with pregestational types of diabetes mellitus, the sFlt-1 / PlGF ratio was a predictor of preeclampsia already in the early stages of pregnancy. Analysis of the ROC curve showed that the threshold sFlt-1 / PlGF ratio for predicting preeclampsia in pregnant women with diabetes mellitus in the first trimester was 32.5 (sensitivity 92.9%, specificity 50.0%) and in the third trimester 71.8 (sensitivity 85.7%, specificity 82.3%) with AUC 0.78 (95% CI 0.680.88) and 0.89 (95% CI 0.830.95), respectively. In the first trimester, the positive and negative predictive values of the sFlt-1 / PlGF ratio as a predictor of preeclampsia in pregnant women with diabetes mellitus were 63.3% and 97.6%, respectively; in the third trimester, 38.9% and 93.6%, respectively. CONCLUSIONS: Blood level alterations of PlGF and sFlt-1 are characteristic of patients with diabetes mellitus in the first and third trimesters of pregnancy. An increase in the sFlt-1 / PlGF ratio is associated with a higher incidence of unfavorable perinatal outcomes in women with impaired carbohydrate metabolism. Determination of the sFlt-1 / PlGF ratio is a valid method for predicting the development or absence of preeclampsia in women with diabetes mellitus.

2019 ◽  
Vol 4 (2) ◽  
pp. 56-60
Author(s):  
Malihe Mohammadi ◽  
Seyedeh Solmaz Moosavi

Introduction: The association between the incidence of glutamic acid decarboxylase antibodies(GADAs) and risk of diabetes in pregnant women is controversial. Here, our aim was to investigate the incidence and clinical relevance of GADA and its association with development of post-delivery diabetes in women with gestational diabetes mellitus (GDM).Methods: This cohort study was conducted in Torbat–e Heydarieh (Khorasan Razavi, Iran) from October 2015 to March 2017. A total of 147 pregnant women with GDM were included in case group. The control group consisted of 147 healthy controls. A GAD diagnostic kit (Diametra Co.,Italy) was used for diagnosis of GADA. The history of insulin therapy and the development of diabetes one year after delivery were investigated.Results: Of 147 pregnant women with GDM, 9 (6.1%) had GADA in their sera. 14.3% (21 out of 147) of women with GDM had history of insulin therapy. 33.3% (7 of 21) of women who had received insulin developed diabetes one year after delivery. Type 1 and type 2 diabetes were observed in, respectively, 1 (0.7%) and 7 (4.8%) of women with GDM at one year after delivery.At one year after delivery, no women in GADA negative women was diagnosed with type 1 diabetes. However, type 2 diabetes was observed in 2.9% of GADA negative pregnant women.Type 1 and type 2 diabetes were also noticed in, respectively, 11.1% and 33.3% of GADA positive mothers at one year after delivery.Conclusion: The prevalence of GADA was 6.1% in diabetic pregnant women. The GADA positivity and history of insulin therapy during pregnancy were significant risk factors for diabetes at one year after delivery. In addition, development of type 1 diabetes was higher in GADA positive pregnant women with GDM than GADA negative women.


Rheumatology ◽  
2021 ◽  
Author(s):  
Rugina I Neuman ◽  
Hieronymus T W Smeele ◽  
A H Jan Danser ◽  
Radboud J E M Dolhain ◽  
Willy Visser

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.


2021 ◽  
Author(s):  
Wenqian Lu ◽  
Mingjuan Luo ◽  
Xiangnan Fang ◽  
Rong Zhang ◽  
Mengyang Tang ◽  
...  

Abstract Background: Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, can lead to morbidity and mortality in both the mother and the infant. Metabolomics has provided new insights into the pathology of GDM and systemic analysis of GDM with metabolites is required for providing more clues for GDM diagnosis and mechanism research. This study aims to reveal metabolic differences between normal pregnant women and GDM patients in the second- and third-trimester stages and to confirm the clinical relevance of these new findings.Methods: Metabolites were quantitated with the serum samples of 200 healthy pregnant women and 200 GDM women in the second trimester, 199 normal controls, and 199 GDM patients in the third trimester. Both function and pathway analyses were applied to explore biological roles involved in the two sets of metabolites. Then the trimester stage-specific GDM metabolite biomarkers were identified by combining machine learning approaches, and the logistic regression models were constructed to evaluate predictive efficiency. Finally, the weighted gene co-expression network analysis method was used to further capture the associations between metabolite modules with biomarkers and clinical indices. Results: This study revealed that 57 differentially expressed metabolites (DEMs) were discovered in the second-trimester group, among which the most significant one was 3-methyl-2-oxovaleric acid. Similarly, 72 DEMs were found in the third-trimester group, and the most significant metabolites were ketoleucine and alpha-ketoisovaleric acid. These DEMs were mainly involved in the metabolism pathway of amino acids, fatty acids and bile acids. The logistic regression models for selected metabolite biomarkers achieved the area under the curve values of 0.807 and 0.81 for the second- and third-trimester groups. Furthermore, significant associations were found between DEMs/biomarkers and GDM-related indices. Conclusions: Metabolic differences between healthy pregnant women and GDM patients were found. Associations between biomarkers and clinical indices were also investigated, which may provide insights into pathology of GDM.


Author(s):  
Süleyman Akarsu ◽  
Filiz Akbiyik ◽  
Eda Karaismailoglu ◽  
Zeliha Gunnur Dikmen

AbstractThyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women.Serum samples were collected from 220 non-pregnant women (age: 18–48), and 2460 pregnant women (age: 18–45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer.GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49–2.33 mIU/L, 10.30–18.11 pmol/L and 3.80–5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51–3.44 mIU/L, 10.30–18.15 pmol/L and 3.69–5.90 pmol/L. GRIs for third trimester pregnancies were 0.58–4.31 mIU/L, 10.30–17.89 pmol/L and 3.67–5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals.TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.


Author(s):  
Saurabh Arora ◽  
Neeraj Kumar Agrawal ◽  
Dhananjaya Melkunte Shanthaiah ◽  
Ashish Verma ◽  
Sanjay Singh ◽  
...  

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Wenqian Lu ◽  
Mingjuan Luo ◽  
Xiangnan Fang ◽  
Rong Zhang ◽  
Shanshan Li ◽  
...  

Abstract Background Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, can lead to morbidity and mortality in both the mother and the infant. Metabolomics has provided new insights into the pathology of GDM and systemic analysis of GDM with metabolites is required for providing more clues for GDM diagnosis and mechanism research. This study aims to reveal metabolic differences between normal pregnant women and GDM patients in the second- and third-trimester stages and to confirm the clinical relevance of these new findings. Methods Metabolites were quantitated with the serum samples of 200 healthy pregnant women and 200 GDM women in the second trimester, 199 normal controls, and 199 GDM patients in the third trimester. Both function and pathway analyses were applied to explore biological roles involved in the two sets of metabolites. Then the trimester stage-specific GDM metabolite biomarkers were identified by combining machine learning approaches, and the logistic regression models were constructed to evaluate predictive efficiency. Finally, the weighted gene co-expression network analysis method was used to further capture the associations between metabolite modules with biomarkers and clinical indices. Results This study revealed that 57 differentially expressed metabolites (DEMs) were discovered in the second-trimester group, among which the most significant one was 3-methyl-2-oxovaleric acid. Similarly, 72 DEMs were found in the third-trimester group, and the most significant metabolites were ketoleucine and alpha-ketoisovaleric acid. These DEMs were mainly involved in the metabolism pathway of amino acids, fatty acids and bile acids. The logistic regression models for selected metabolite biomarkers achieved the area under the curve values of 0.807 and 0.81 for the second- and third-trimester groups. Furthermore, significant associations were found between DEMs/biomarkers and GDM-related indices. Conclusions Metabolic differences between healthy pregnant women and GDM patients were found. Associations between biomarkers and clinical indices were also investigated, which may provide insights into pathology of GDM.


Author(s):  
Masoomeh Shirzaiy ◽  
Zohreh Dalirsani

Abstract Objectives During pregnancy, systemic physiological alterations lead to some changes in the oral cavity, which could prepare the mouth environment for oral and dental problems. This study was aimed to investigate salivary α-amylase, sialic acid levels, and pH levels in pregnant and nonpregnant females. Materials and Methods In this analytical, case–control study, unstimulated saliva samples were collected with spiting method from 35 pregnant women (case group) and 35 nonpregnant women (control group) and transferred to the laboratory to assess salivary α-amylase, sialic acid, and pH levels. Data were analyzed by SPSS (version: 19) software through statistical methods of independent t-test and analysis of variance. Results The mean sialic acid levels were 2.285 ± 1.230 mg/dL in pregnant and 2.744 ± 1.326 in nonpregnant women without any significant difference (p = 0.138). The mean salivary α-amylase concentrations were 2.461 ± 1.869 U/L and 2.439 ± 2.058 U/L, respectively, in pregnant and nonpregnant women, with no significant difference (p = 0.963).The mean salivary pH in nonpregnant women was significantly more than that in pregnant women (7.845 ± 0.430 and 6.868 ± 0.413, respectively) (p < 0.001). Also, the mean salivary pH levels in pregnant women were 7.474 ± 0.420 in the first trimester, 6.868 ± 0.413 in the second trimester, and 6.568 ± 0.387 in the third trimester, which were significantly different (p < 0.001). Conclusion Salivary sialic acid and α-amylase levels among pregnant women were no different from those of other subjects. During pregnancy, the salivary pH significantly reduced, and the mean salivary pH during pregnancy had a decreasing trend from the first trimester to the third trimester.


Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1332-1338 ◽  
Author(s):  
A Estelles ◽  
J Gilabert ◽  
J Aznar ◽  
DJ Loskutoff ◽  
RR Schleef

This report defines the nature of the molecules responsible for the increased plasma plasminogen activator inhibitor (PAI) activity in preeclamptic patients and the relationship of these inhibitors to the severity of placental damage in preeclampsia. Clinical groups consisting of pregnant women with either severe preeclampsia or chronic hypertension with superimposed severe preeclampsia, as well as normal pregnant and nonpregnant women, were analyzed in a panel of functional and immunologic assays for PAI-1 and PAI-2. Pure severe preeclamptic patients in their third trimester showed a significant increase in both antigenic (136 ng/mL) and functional (5.76 U/mL) type 1 PAI (PAI-1) as compared with normal third-trimester pregnant women (34.8 ng/mL and 2.57 U/mL, respectively). In contrast, antigenic (186 ng/mL) and functional (5.76 U/mL) levels of type 2 PAI (PAI-2) were significantly lower in the pure severe preeclampsia group as compared with the values of the normal pregnant group (269 ng/mL and 9.58 U/mL, respectively). The patients with chronic hypertension and superimposed severe preeclampsia exhibited PAI-2 levels comparable to those of the pure preeclamptic group, whereas their antigenic and functional PAI-1 levels were intermediate (94 ng/mL and 3.25 U/mL, respectively) between the normal pregnant and the pure preeclamptic groups. During early puerperium of both normal pregnant women and patients, plasma PAI-1 antigen and activity decreased within one day to approximately the levels detected in normal nonpregnant women, while PAI-2 levels remained elevated for over 11 days. Similar results were obtained in plasma samples obtained from citrated blood and blood collected with an anticoagulant/antiplatelet mixture, suggesting that increased PAI-1 levels in preeclamptic patients were not due to platelet activation in vitro. In preeclamptic patients, a positive correlation between birth weight and PAI-2 values was observed (r = .64, P less than .05), whereas birth weight was inversely correlated with both PAI-1 levels and total PAI activity (r = -.6, P less than .005 and r = -.76, P less than .005 respectively). Preeclamptic patients with extensive placental infarction exhibited higher plasma PAI activity (24.1 U/mL v 11.6 U/mL) and PAI-1 values (305 ng/mL v 80.9 ng/mL) than preeclamptic patients without extensive placental infarction. In contrast, PAI-2 levels were reduced in preeclamptic patients with infarction in comparison with those of patients without infarction (141 ng/mL v 212.9 ng/mL). Our data indicate that increases in the level of PAI-1 accounts for the high plasma PAI activity in severe preeclampsia as measured using single-chain t-PA.


2020 ◽  
Author(s):  
Zhengyuan Wang ◽  
Yiwen Wu ◽  
Zehuan Shi ◽  
Jun Song ◽  
Guoquan Wang ◽  
...  

Abstract Background: China’s universal salt-iodization program has all but eliminated iodine deficiency disorders. Concern has shifted to mild iodine deficiency. Our study examined factors with the potential to predict mild iodine deficiency in pregnant women. Methods: A total of 2 400 pregnant women were enrolled using a multistage, stratified, random-sampling method. Data were collected through face-to-face interviews, a standardized questionnaire, an iodine-related knowledge questionnaire, urine samples, and household cooking salt samples. Results: The median urinary iodine concentration (MUIC) was 148.0 μg/L for all participants, and 155.0 μg/L, 151.0 μg/L, and 139.6 μg/L in the first, second, and third trimesters, respectively. The third trimester’s MUIC was significantly lower than that of the first trimester, and the usage rates of iodized salt and qualified-iodized salt were 71.5% and 59.4%, respectively. Iodine-related knowledge was significantly different between the high and low UIC groups. Participants’ MUIC increased significantly with increases in iodine-related knowledge. The third trimester was a significant risk factor for high UIC, whereas abundant iodine-related knowledge, study the dietary knowledge urgently, and consumption of iodine-rich food within 48 hours of a urine iodine test were significant protective factors for high UIC (P<0.05). Conclusions: Iodine levels are adequate among pregnant women in Shanghai during the first and second trimesters, but insufficient in the third trimester. The use of iodized cooking salt does not determine the iodine status of pregnant women. Abundant iodine-related knowledge is important for pregnant women in the third trimester to maintain adequate urinary iodine.


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