The Association of Hematological Parameters in Early and Middle Pregnancy with the Risk of Gestational Diabetes Mellitus.

Objective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6-12 weeks of gestation) to the second trimester (24-28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.

Relationship between serum uric acid in early pregnancy and gestational diabetes mellitus: a prospective cohort study.

PURPOSE: The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. METHODS: A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. RESULTS: The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) µmol/l vs. 201.9(176.0, 232.0) µmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 µmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. CONCLUSION: The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. CLINICAL TRIAL NUMBER: NCT03246295.

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Pregnant Chinese Women.

INTRODUCTION: This study aimed to develop a simplified screening model to identify pregnant Chinese women at risk of gestational diabetes mellitus (GDM) in the first trimester. METHODS: This prospective study included 1289 pregnant women in their first trimester (6-12 weeks of gestation) with clinical parameters and laboratory data. Logistic regression was performed to extract coefficients and select predictors. The performance of the prediction model was assessed in terms of discrimination and calibration. Internal validation was performed through bootstrapping (1000 random samples). RESULTS: The prevalence of GDM in our study cohort was 21.1%. Maternal age, prepregnancy body mass index (BMI), a family history of diabetes, fasting blood glucose levels, the alanine transaminase to aspartate aminotransferase ratio (ALT/AST), and the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were selected for inclusion in the prediction model. The Hosmer-Lemeshow goodness-of-fit test showed good consistency between prediction and actual observation, and bootstrapping indicated good internal performance. The area under the receiver operating characteristic curve (ROC-AUC) of the multivariate logistic regression model and the simplified clinical screening model was 0.825 (95% confidence interval [CI] 0.797-0.853, P < 0.001) and 0.784 (95% CI 0.750-0.818, P < 0.001), respectively. The performance of our prediction model was superior to that of three other published models. CONCLUSION: We developed a simplified clinical screening model for predicting the risk of GDM in pregnant Chinese women. The model provides a feasible and convenient protocol to identify women at high risk of GDM in early pregnancy. Further validations are needed to evaluate the performance of the model in other populations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03246295.

ALT/AST as an Independent Risk Factor of Gestational Diabetes Mellitus Compared with TG/HDL-C.

OBJECTIVE: This study aimed to find the association between alanine transaminase-to-aspartate aminotransferase ratio (ALT/AST) and the incidence of gestational diabetes mellitus (GDM). METHODS: A total of 1128 pregnant women were included in this prospective, double-center, observational cohort study. ALT, AST and total bilirubin (TBil) were tested during 6-12 weeks of gestation and 75-g oral glucose tolerance test (OGTT) was conducted during 24-28 weeks of gestation to screen GDM. The association between ALT/AST and glucose concentration during OGTT was analyzed by linear regression model. The OR with 95% CI for incidence of GDM associated with ALT/AST was estimated by binary logistic regression. The discriminatory values of ALT/AST and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) for GDM were calculated by the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: The incidence of GDM was 22.07% (249/1128). ALT/AST was higher in GDM group than in NGT group (0.92 [0.75, 1.18] vs 0.80[0.65, 1.02], P <0.001). ALT/AST had positive correlations with fasting blood glucose, 1-hour and 2-hour blood glucose concentration during OGTT (0.089 [95% CI: 0.034, 0.163], 0.176 [95% CI: 0.052, 0.104], and 0.115 [95% CI: 0.199, 0.609], respectively). The OR of ALT/AST for incidence of GDM was 1.603 (95% CI:1.097, 2.344). The ROC-AUC of ALT/AST and TG/HDL-C reached 0.615 (95% CI: 0.575, 0.655) and 0.619 (95% CI: 0.580, 0.659), respectively. CONCLUSION: ALT/AST in early pregnancy was an independent risk factor of GDM. The predictive ability of ALT/AST was similar to TG/HDL-C for GDM.

HOMA-IR as a risk factor of gestational diabetes mellitus and a novel simple surrogate index in early pregnancy.

OBJECTIVE: To assess the association between insulin resistance and gestational diabetes mellitus (GDM) in early pregnancy and find a simple surrogate index of the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: A total of 700 pregnant women were included in this prospective, double-center, observational cohort study. The glucose and lipid metabolic characterization was performed at 6-12 weeks of pregnancy. All participants underwent a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. Linear regression analysis was applied to find a novel surrogate index of HOMA-IR. Binary logistic analysis was applied to estimate possible associations of different indices with GDM and insulin resistance. RESULTS: GDM was diagnosed in 145 of 700 women with singleton pregnancies (20.7%). HOMA-IR was higher in the GDM group than in the normal glucose tolerance (NGT) group and was an individual risk factor for GDM (adjusted risk ratio RR 1.371, 95% confidence interval [CI] 1.129-1.665, P < 0.001). TyHGB index as the surrogate index of HOMA-IR was represented as TG/HDL-C + 0.7*FBG (mmol/L) +0.1*preBMI (kg/m2 )(where TG/HDL-C is triglyceride/high-density lipoprotein cholesterol; FBG is fasting blood glucose, and preBMI is the pre-pregnancy body mass index [calculated as weight in kilograms divided by the square of height in meters]). The cut-off point of the TyHGB index was 6.0 (area under the curve 0.827, 95% CI 0.794-0.861, P < 0.001) for mild insulin resistance. CONCLUSION: Increased HOMA-IR in early pregnancy was a risk factor of GDM. TyHGB index could be a surrogate index of HOMA-IR and had a predictive value for GDM.

Predictability of HOMA-IR for Gestational Diabetes Mellitus in Early Pregnancy Based on Different First Trimester BMI Values.

Objective: To investigate the ability of homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy for predicting gestational diabetes mellitus (GDM) in Chinese women with different first-trimester body mass index (FT-BMI) values. Methods: Baseline characteristics and laboratory tests were collected at the first prenatal visit (6−12 weeks of gestation). GDM was diagnosed by a 75 g oral glucose tolerance test (OGTT) at 24−28 weeks of gestation. Partial correlation analysis and binary logistic regression were applied to identify the association between HOMA-IR and GDM. The cutoff points for predicting GDM were estimated using receiver operating characteristic (ROC) curve analysis. Results: Of the total of 1343 women, 300 (22.34%) were diagnosed with GDM in the 24−28 weeks of gestation. Partial correlation analysis and binary logistic regression verified HOMA-IR as a significant risk factor for GDM in the normal weight subgroup (FT-BMI < 24 kg/m2) (adjusted OR 2.941 [95% CI 2.153, 4.016], P < 0.001), overweight subgroup (24.0 kg/m2 ≤ FT-BMI < 28.0 kg/m2) (adjusted OR 3.188 [95% CI 2.011, 5.055], P < 0.001), and obese subgroup (FT-BMI ≥ 28.0 kg/m2) (adjusted OR 9.415 [95% CI 1.712, 51.770], p = 0.01). The cutoff values of HOMA-IR were 1.52 (area under the curve (AUC) 0.733, 95% CI 0.701−0.765, p < 0.001) for all participants, 1.43 (AUC 0.691, 95% CI 0.651−0.730, p < 0.001) for normal weight women, 2.27 (AUC 0.760, 95% CI 0.703−0.818, p < 0.001) for overweight women, and 2.31 (AUC 0.801, 95% CI 0.696−0.907, p < 0.001) for obese women. Conclusions: Increased HOMA-IR in early pregnancy is a risk factor for GDM, and HOMA-IR can be affected by body weight. The cutoff value of HOMA-IR to predict GDM should be distinguished by different FT-BMI values.

The Predictive Ability of Hepatic Steatosis Index for Gestational Diabetes Mellitus and Large for Gestational Age Infant Compared with Other Noninvasive Indices Among Chinese Pregnancies: A Preliminary Double-center Cohort Study.

OBJECTIVE: To evaluate the association of hepatic steatosis index (HSI) in the first trimester and the risk of gestational diabetes mellitus (GDM) as well as large for gestational age (LGA) infant in Chinese women. METHODS: A total of 1082 pregnant women were included in this study. Maternal basic laboratory data, including ALT, AST, FBG, insulin, TG, and HDL-C, were tested during 6-12 weeks of gestation and anthropometric characteristics were monitored during gestation. A 75-g oral glucose tolerance test (OGTT) was conducted at 24-28 weeks of gestation. HSI, nonalcoholic fatty liver disease (NAFLD) liver fat score, triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) and triglyceride-glucose (TyG) index were calculated. Odds ratio with 95% confidence interval for subsequent risk of GDM and LGA by HSI quartiles were assessed by binary logistic regression model. The predictive ability of HSI for GDM and LGA was evaluated by the receiver operating characteristic (ROC) curve analysis and was compared with other indices. RESULTS: The incidence of GDM and LGA were 22.09% (239/1082) and 10.53% (87/826). HSI was higher in GDM group than in NGT group (median, interquartile range: 30.67, 27.20-35.10 vs 27.98, 25.70-30.82, P<0.001). Incidence of GDM was gradually increased with increasing HSI values. Women in the highest HSI quartile had significantly higher risk of LGA delivery than those in the lowest HSI quartile (P<0.05). The area under the ROC curves of HSI for GDM and LGA were higher than other indices, reaching 0.646 (95%CI: 0.605-0.686) and 0.600 (95%CI: 0.541-0.660), respectively. CONCLUSION: Higher HSI was independently associated with higher risk of GDM and LGA in Chinese women. HSI in the first trimester can predict the risk of GDM and LGA.

Effect of lesion location on endometriotic adhesion and angiogenesis in SCID mice.

OBJECTIVE: To evaluate the effects of lesion location on adhesion and angiogenesis of transplanted endometriotic lesions in SCID mice. METHODS: Three groups of female SCID mice included intraperitoneal (i.p.) (n = 12), subcutaneous (s.c.) (n = 12), and mock surgery (control) (n = 12). At 2 weeks after ovariectomy, the mice were transplanted with eutopic endometrium from endometriosis patients either subcutaneously or sutured within the peritoneal, or underwent mock surgery. After 4 weeks, the mice were sacrificed to evaluate the adhesion and volume changes of the implanted lesions. Furthermore, semiquantitative immunohistochemical staining was performed to analyze expression of MMP-2 and TIMP-2 as adhesion makers, and vWF, VEGF, and HIF-1α as angiogenesis markers. RESULTS: Adhesion occurred in 9 of 12 mice in the i.p. group, 3 of 12 mice in the s.c. group, and 3 of 12 mice in the control group. Fisher's exact test showed that the difference of adhesion occurrence between i.p. and s.c. groups was statistically significant (p < 0.05). Graft volume changes were higher in the s.c. group than those in the i.p. group. MMP-2 expression was higher in the s.c. group than that in the i.p. group (p < 0.01). There was no significant difference of TIMP-2 expression between s.c. and i.p. groups. vWF, VEGF, and HIF-1α expression was significantly higher in the s.c. group than that in the i.p. group (p < 0.01). CONCLUSIONS: Lesion location might be involved in the pathological changes of endometriosis. The intraperitoneal location is related to endometriotic adhesion, whereas the subcutaneous location is related to the infiltration of endometriotic lesions.

Effect of oxygen tensions on the proliferation and angiogenesis of endometriosis heterograft in severe combined immunodeficiency mice.

OBJECTIVE: To investigate the effects of oxygen on the proliferation and angiogenesis of endometriosis in vivo. DESIGN: Animal studies. SETTING: Animal research facility. ANIMAL(S): Thirty-six female severe combined immunodeficiency (SCID) mice, implanted with eutopic endometrium from seven endometriosis patients. INTERVENTION(S): Human eutopic endometrial tissues were randomized to normoxia, hyperoxia, or hypoxia pretreatment and were subcutaneously implanted into estrogen-treated ovariectomized SCID mice. MAIN OUTCOME MEASURE(S): The growth and quality of the implants were measured, and the expression of proliferation- and angiogenesis-associated markers (i.e., Ki67, CD31, vascular endothelial growth factor, and hypoxia-inducible factor-1α) were assessed using immunohistochemistry and Western blot analyses. RESULT(S): The growth curves of the implants were distinct with different oxygen pretreatments. The growth of the implants of the hypoxia group was significantly increased compared with the normoxia group, but the growth of the implants of the hyperoxia group was significantly decreased compared with the normoxia group. Microscopic examination indicated that lesions with hyperplastic cylindrical glandular epithelium were surrounded by the endometrial stroma in the hypoxia group, but the glandular epithelium was partially depauperate in the hyperoxia group. The expression of Ki67, CD31, vascular endothelial growth factor, and hypoxia-inducible factor-1α in the hypoxia-pretreated implants was significantly higher compared with the hyperoxia or normoxia groups. CONCLUSION(S): Oxygen can alter the growth patterns of endometriosis implants in a SCID mouse model. Hypoxia pretreatment promoted the proliferation and angiogenesis of endometriosis, whereas hyperoxia pretreatment exhibited the opposite effect.

[Analysis of related factors of premature delivery for the migrant population in local suburban Beijing areas].

OBJECTIVE: To study the health conditions of pregnant migrant women in some suburban areas of Beijing by comparing a variety of pathological, physiological and social factors and exploring the relevant factors associated with preterm birth so as to prevent effectively preterm birth. METHODS: A total of 279 cases of pregnancy in preterm birth at out hospital from January 2004 to December 2008 were reviewed. The date of maternal age, parity, prenatal examinations, history of vaginitis, history of chorioamnionitis, premature rupture of membranes, occupation, residing location and education status were recorded. And the relationship between them and preterm birth were analyzed by χ(2) test. RESULTS: The overall incidence of preterm birth was 5.34%. And the following factors had statistically significant differences with premature birth: chorioamnionitis, vaginitis, premature rupture of membranes, a lack of prenatal examinations, low education status, migrant population or maternal parity. However there was no statistical significance (P > 0.05) between preterm birth and other factors, such as occupation. CONCLUSION: The incidence of preterm birth is associated with a lack of prenatal examinations, low education status, chorioamnionitis, bacterial vaginitis and premature rupture of membranes. Therefore the migrant women in Beijing should receive targeted education programs during pregnancy. And reproductive tract inflammation should be properly treated.

[Study of factors associated with subclinical chorioamnionitis in term pregnancy].

OBJECTIVE: To investigate the effects of various factors upon subclinical chorioamnionitis (SCCAS) during pregnancy and delivery. METHODS: A total of 796 cases of pregnancy in full-term birth at our hospital from December 2006 to December 2008 were reviewed. The data of maternal age, gravidity, parity, gestational age, prenatal care, history of vaginitis, premature rupture of membranes, occupation, educational status and delivery mode were recorded. And then the relationship between one of them and chorioamniotis were analyzed by chi(2) test. RESULTS: The overall incidence of SCCAS was 39.95% in full-term birth. The pregnant women, who had no prenatal care or no occupation, or had a history of vaginitis or premature rupture of membranes, were found to have a higher incidence (P < 0.05 or P < 0.01). However, there were no statistical significance (P > 0.05) between SCCAS and other seven factors, such as gravida age, gravidity, parity, gestational age, educational status, delivery mode and living conditions. CONCLUSION: Women with full-term birth, even in the absence of symptoms, may have already suffered from acute or chronic chorioamnionitis. The incidence is associated with prenatal care, history of vaginitis and premature rupture of membranes.