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Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies.

ABSTRACT: Background: If not detected and treated, gestational diabetes mellitus (GDM) can cause serious pregnancy complications such as macrosomia, preeclampsia, and fetal/neonatal mortality. Many studies have examined underlying contributing factors for GDM, including hypercoagulation. Factor XII (FXII) is a coagulation factor that increases throughout normal pregnancies, and we evaluated the relationship of GDM with FXII, FXIIa (activated FXII), and other coagulation parameter levels. GDM and macrosomia are closely related, but it is not known whether FXII could be an independent causal factor for macrosomia.

Methods: In this prospective study, blood samples were taken from 69 pregnant women at the time of term delivery to determine levels of FXII, FXIIa, and other coagulation parameters. Based on the results, pregnancies fell into GDM, non-diabetic with macrosomia (M), or healthy (C [control]).

Results: FXII concentration levels were significantly higher in GDM patients compared with the M and C groups. There were no significant differences when comparing FXIIa, activated partial thromboplastin time, prothrombin time (PT), and international normalized ratio. The GDM group saw a significant negative correlation between FXII concentrations and maternal pregestational body mass index (BMI) and BMI before delivery. In the M group, a positive correlation was observed between FXII concentrations and newborn weight and newborn weight percentile.

Conclusions: An increase in FXII levels was observed in patients with gestational diabetes. Associations between coagulation parameters and GDM should be further analyzed to define the mechanisms of GDM and possible treatment modalities.

Trial registration: Our study has been registered at clinicaltrials.gov ( NCT03583216 ). Registered on July 11, 2018.

SUBMITTER: Ozbasli E

PROVIDER: S-EPMC7709445 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies.

Ozbasli Esra E Takmaz Ozguc O Karabuk Emine E Gungor Mete M

BMC pregnancy and childbirth 20201202 1

<h4>Background</h4>If not detected and treated, gestational diabetes mellitus (GDM) can cause serious pregnancy complications such as macrosomia, preeclampsia, and fetal/neonatal mortality. Many studies have examined underlying contributing factors for GDM, including hypercoagulation. Factor XII (FXII) is a coagulation factor that increases throughout normal pregnancies, and we evaluated the relationship of GDM with FXII, FXIIa (activated FXII), and other coagulation parameter levels. GDM and ma ...[more]

PMID: 33267793

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Project description:Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy. GDM is associated with serious maternal and fetal complications, in particular, fetal macrosomia and large for gestational age (LGA), which predisposes to a higher risk of childhood obesity and type 2 diabetes mellitus later in life. Early prediction and diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. Glycated haemoglobin A1c (HbA1c) has been widely used for monitoring, screening for and diagnosing diabetes and prediabetes. Increasing evidence has also showed that HbA1c could indicate fetal glucose supply. Thus, we hypothesise that the HbA1c level at around 24 to 28 weeks may predict the development of fetal macrosomia or an LGA baby in women with GDM, which could be useful for better prevention of fetal macrosomia and LGA. We searched MEDLINE, EMBASE, Cochrane and Google Scholar databases from inception to November 2022 for relevant studies that reported at least one HbA1c level during 24-28 weeks of pregnancy and fetal macrosomia or an LGA baby. We excluded studies that were not published in the English language. No other search filters were applied during the search. Two independent reviewers selected eligible studies for meta-analysis. Two independent reviewers performed data collection and analyses. The PROSPERO registration number is CRD42018086175. A total of 23 studies were included in this systematic review. Of these, 8 papers reported data of 17,711 women with GDM that allowed for inclusion in a meta-analysis. The obtained results demonstrated the prevalence of fetal macrosomia was 7.4% and of LGA, 13.36%. Meta-analyses showed that the estimated pooled risk ratio (RR) for LGA in women with high HbA1c values compared to normal or low values was 1.70 (95% CI: 1.23-2.35), p = 0.001; and the pooled RR for fetal macrosomia was 1.45 (95% CI: 0.80 to 2.63), p = 0.215. Further research is needed to evaluate the utility of HbA1c levels in predicting the delivery of a baby with fetal macrosomia or LGA in pregnant women.

Project description:BackgroundThird trimester fetal anthropometric parameters are known to predict neonatal complications. A better understanding of predictors of adverse fetal parameters might help to personalize the use and frequency of fetal ultrasound. The objectives of this study were: (a) to evaluate the utility of maternal sociodemographic, anthropometric and metabolic predictors to predict 3rd trimester fetal anthropometric parameters in women with gestational diabetes mellitus (GDM), (b) to assess whether the impact of these maternal predictors is fetal sex-dependent, and (c) to provide a risk stratification for markers of fetal overgrowth (fetal weight centile (FWC) and fetal abdominal circumference centile (FACC) depending on prepregnancy BMI and gestational weight gain (GWG) until the 1st GDM visit.MethodsThis prospective study included 189 women with GDM. Maternal predictors were age, ethnicity, prepregnancy BMI, GWG and excessive weight gain until the 1st GDM visit, fasting, 1-hour and 2-hour blood glucose oral glucose tolerance test values, HbA1c at the 1st visit and medical treatment requirement. Fetal outcomes included FWC, FWC >90% and <10%, FACC, FACC >90% and <10%, at 29 0/7 to 35 6/7 weeks of gestational age. We performed univariate and multivariate regression analyses and probability analyses.ResultsIn multivariate analyses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC. GWG until the 1st GDM visit was associated with FWC, FACC and FACC > 90% (all p ≤ 0.045). Other maternal parameters were not significantly associated with fetal anthropometry in multivariate analyses (all p ≥ 0.054). In female fetuses, only GWG was associated with FACC (p= 0.044). However, in male fetuses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC and GWG with FWC in multivariate analyses (all p ≤ 0.030). In women with a prepregnancy BMI of ≥ 25 kg/m2 and a GWG until the 1st GDM visit ≥ 10.3 kg (mean GWG), the risk for FWC > 90% and FACC > 90% was 5.3 and 4 times higher than in their counterparts.ConclusionsA personalized fetal ultrasound surveillance guided by fetal sex, prepregnancy BMI and GWG may be beneficial in reducing adverse fetal and neonatal outcomes.

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Project description:BackgroundGestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B12, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM.ResultsIn this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25-33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = - 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = - 0.13, p = 0.049 and r = - 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = - 0.28, p = 0.015).ConclusionsIn conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.

Project description:IntroductionGestational diabetes mellitus (GDM), a metabolism-related pregnancy complication, is significantly associated with an increased risk of macrosomia. We hypothesized that maternal circulating metabolic biomarkers differed between women with GDM and macrosomia (GDM-M) and women with GDM and normal neonatal weight (GDM-N), and had good prediction performance for GDM-M.MethodsPlasma samples from 44 GDM-M and 44 GDM-N were analyzed using Olink Proseek multiplex metabolism assay targeting 92 biomarkers. Combined different clinical characteristics and Olink markers, LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomogram was developed based on the selected variables visually. Receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used to validate the model.ResultsWe found 4 metabolism-related biomarkers differing between groups [CLUL1 (Clusterin-like protein 1), VCAN (Versican core protein), FCRL1 (Fc receptor-like protein 1), RNASE3 (Eosinophil cationic protein), FDR < 0.05]. Based on the different clinical characteristics and Olink markers, a total of nine predictors, namely pre-pregnancy body mass index (BMI), weight gain at 24 gestational weeks (gw), parity, oral glucose tolerance test (OGTT) 2 h glucose at 24 gw, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw, were identified by LASSO regression. The model constructed using these 9 predictors displayed good prediction performance for GDM-M, with an area under the ROC of 0.970 (sensitivity = 0.955, specificity = 0.886), and was well calibrated (P Hosmer-Lemeshow test = 0.897).ConclusionThe Model included pre-pregnancy BMI, weight gain at 24 gw, parity, OGTT 2 h glucose at 24 gw, HDL and LDL at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw had good prediction performance for predicting macrosomia in women with GDM.

Dataset Information

Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies.

Publications

Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies.

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