Low thyroid hormone levels in early pregnancy are a risk factor for GDM incidence.

Context Accurate methods for early gestational diabetes mellitus (GDM) (during the first trimester of pregnancy) prediction in Chinese and other populations are lacking. Objectives This work aimed to establish effective models to predict early GDM. Methods Pregnancy data for 73 variables during the first trimester were extracted from the electronic medical record system. Based on a machine learning (ML)-driven feature selection method, 17 variables were selected for early GDM prediction. To facilitate clinical application, 7 variables were selected from the 17-variable panel. Advanced ML approaches were then employed using the 7-variable data set and the 73-variable data set to build models predicting early GDM for different situations, respectively. Results A total of 16 819 and 14 992 cases were included in the training and testing sets, respectively. Using 73 variables, the deep neural network model achieved high discriminative power, with area under the curve (AUC) values of 0.80. The 7-variable logistic regression (LR) model also achieved effective discriminate power (AUC = 0.77). Low body mass index (BMI) (≤ 17) was related to an increased risk of GDM, compared to a BMI in the range of 17 to 18 (minimum risk interval) (11.8% vs 8.7%, P = .09). Total 3,3,5′-triiodothyronine (T3) and total thyroxin (T4) were superior to free T3 and free T4 in predicting GDM. Lipoprotein(a) was demonstrated a promising predictive value (AUC = 0.66). Conclusions We employed ML models that achieved high accuracy in predicting GDM in early pregnancy. A clinically cost-effective 7-variable LR model was simultaneously developed. The relationship of GDM with thyroxine and BMI was investigated in the Chinese population.

Context Previous studies suggest that maternal thyroid function affects fetal growth, but the association between combined thyroid hormones from early to late pregnancy and newborn birth weight remains unknown. Objective To explore the association of maternal thyroid function during early and late pregnancy with birth weight. Design A large prospective cohort study of a Chinese population. Setting This study recruited pregnant women who underwent first-trimester prenatal screenings at the International Peace Maternity and Child Health Hospital between January 2013 and December 2016. Participants This study enrolled 46,186 mothers in whom TSH, free thyroxine (FT4), T3, and thyroid peroxidase antibody concentrations were measured in the first and third trimesters and in whom data on birth weight were available. Main Outcome Measures Birth weight, small for gestational age, large for gestational age (LGA). Results A higher TSH or FT4 concentration, or a lower T3 concentration, during the first or third trimester was associated with a lower birth weight. The lowest percentiles of maternal FT4 (FT4 < 2.5th percentile) in both trimesters were associated with a 0.34-SD higher birth weight. The effect estimates were greater in those in the first trimester (0.23 SD) or in the third trimester (0.17 SD). The association of maternal TSH and FT4 with birth weight differed according to fetal sex. Conclusions Persistently low FT4 concentrations throughout pregnancy were associated with higher birth weight and an increased risk of LGA. Based on these findings, we recommend monitoring mildly altered concentrations of thyroid hormone throughout pregnancy.

The recommendations for the diagnosis of stage 1 hypertension were recently revised by the American Heart Association primarily based on its impact on cardiovascular disease risks. Whether the newly diagnosed stage 1 hypertension impacts pregnancy complications remain poorly defined. We designed a retrospective cohort study to investigate the associations of stage 1 hypertension detected in early gestation (<20 weeks) with risks of adverse pregnancy outcomes stratified by prepregnancy body mass index. A total of 47 874 women with singleton live births and blood pressure (BP) <140/90 mm Hg were included, with 5781 identified as stage 1a (systolic BP, 130–134 mm Hg; diastolic BP, 80–84 mm Hg; or both) and 3267 as stage 1b hypertension (systolic BP, 135–139 mm Hg; diastolic BP, 85–90 mm Hg; or both). Slightly higher, yet significant, rates and risks of gestational diabetes mellitus, preterm delivery, and low birth weight (<2500 g) were observed in both groups compared with normotensive controls. Importantly, women with stage 1a and stage 1b hypertension had significantly increased incidences of hypertensive disorders in pregnancy compared with normotensive women (adjusted odds ratio, 2.34 [95% CI, 2.16–2.53]; 3.05 [2.78–3.34], respectively). After stratifying by body mass index, stage 1a and 1b hypertension were associated with increased hypertensive disorders in pregnancy risks in both normal weight (body mass index, 18.5–24.9; adjusted odds ratio, 2.44 [2.23–2.67]; 3.26 [2.93–3.63]) and the overweight/obese (body mass index, ≥25; adjusted odds ratio, 1.90 [1.56–2.31]; 2.36 [1.92–2.90]). Current findings suggested significantly increased adverse pregnancy outcomes associated with stage 1 hypertension based on the revised American Heart Association guidelines, especially in women with prepregnancy normal weight.

Background/Aims: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. Methods: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. Results: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3’-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. Conclusion: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

BackgroundThis study investigated the relationship of serum homocysteine in early pregnancy with the risk of gestational hypertension (GH) and preeclampsia (PE) and with the severity of preeclampsia.Material/MethodsIn a retrospective cohort study, we identified 147 confirmed cases of preeclampsia (103 with mild PE and 44 with severe PE) and 147 confirmed cases of GH; 4418 women who remained normotensive and nonproteinuric throughout pregnancy served as controls. Maternal blood samples were collected at between 11 and 13 weeks of gestation to test serum concentrations of homocysteine (Hcy), folic acid, and VitB12. A logistic regression model was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).ResultsWomen who subsequently developed GH and PE were older and had higher body mass indexes (BMIs) than those in the control group. Compared with the control group, women who developed PE were less educated (P=0.031), and more of those who developed GH were primiparas (P=0.012). The serum levels of Hcy in severe PE were significantly higher than those in the control group (median: 8.50 μmol/L vs. 7.33 μmol/L, P<0.001). After logistic regression analyses for potential confounding factors, the adjusted odds ratios (aORs) of Hcy was 1.12 for severe PE (95% CI 1.06–1.20). The serum concentrations of folic acid and VitB12 in those with GH and PE were not significantly different from controls.ConclusionsA high level of Hcy in the first trimester is an independent risk factor for severe PE, although it is not a useful marker for the subsequent development of GH and mild PE.

Although thyroid dysfunction in early pregnancy may have adverse effects on pregnancy outcomes, few studies have examined the relationship between maternal low free thyroxin (FT4) levels in both first and third trimesters of pregnancy and the incidence of adverse pregnancy outcomes. We hypothesized that low FT4 levels in either first or third trimesters of pregnancy may have different effects on pregnancy outcomes. The study included 6,031 mothers who provided both first and third pregnancy serum samples for analyses of thyroid function. Adverse pregnancy outcomes, such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension and preeclampsia, were diagnosed using the oral glucose tolerance test, blood pressure and urine protein test. Serum metabolites like adenosine and its analogues were identified using hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry (MS/MS). The incidence of hypothyroidism in pregnant women tended to increase with age and pre-pregnancy body mass index (BMI). The incidence of GDM was negatively correlated with maternal FT4 levels during early pregnancy while the incidence of preeclampsia was negatively correlated with maternal FT4 levels during late pregnancy. The incidence of pregnancy-induced hypertension was not significantly correlated with maternal FT4 levels. The women who had isolated maternal hypothyroxemia (IMH) in the third trimester of pregnancy had an increased risk of developing preeclampsia. Some metabolites like adenosine and its analogues in the serum were significantly changed in pregnant mothers with IMH. In conclusion, low FT4 levels during pregnancy are a risk factor for GDM and preeclampsia. Adenosine and its analogues may be important bridges between IMH and preeclampsia.

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