Effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of GDM.

To investigate the effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of gestational diabetes mellitus. 3966 pregnant women were enrolled in this study. Multivariate logistic regression analysis was conducted to estimate the relative risk between pre-pregnancy BMI, gestational weight gain, and adverse pregnancy outcome. Pre-pregnancy BMI was found to be a risk factor for preeclampsia (OR = 1.159), gestational diabetes mellitus (OR = 1.191), gestational hypertension (OR = 1.221), and macrosomia (OR = 1.165). Gestational weight gain was a risk factor for preeclampsia (OR = 1.783), placental abruption (OR = 2.209), and macrosomia (OR = 1.506). Total weight gain during pregnancy cannot be used as a predictor of GDM. Pre-pregnancy BMI is a risk factor for gestational diabetes mellitus complicated with preeclampsia, preterm delivery, gestational hypertension, and macrosomia. Impact statementWhat is already known on this subject? Obesity during pregnancy includes pre-pregnancy obesity and excessive weight gain during pregnancy. Obese pregnant women have a higher risk of pregnancy complications.What do the results of this study add? We focus on the effects of pre-pregnancy BMI on pregnancy outcomes, classified by Asian criteria. Our findings suggest for the first time that excessive weight gain during pregnancy is a risk factor for placental abruption and we specifically point out that total weight gain during pregnancy cannot be used as a predictor of GDM.What are the implications of these findings for clinical practice and/or further research? This study is helpful to monitor the risk of adverse pregnancy outcomes in the Asian population and suggest the risk of pregnancy complications, such as gestational diabetes mellitus and placental abruption.

Epidemiological analysis of maternal lipid levels during the second trimester in pregnancy and the risk of adverse pregnancy outcome adjusted by pregnancy BMI.

BACKGROUND: Pregnancy is accompanied by profound changes in lipid metabolism. We aimed to assess whether effects of second trimester body mass index and maternal lipid concentrations are associated with an increased risk of adverse pregnancy outcomes. METHODS: We investigated the serum levels of maternal lipids during the second trimester in pregnancy, and analyzed associations between the lipid levels and the risk of adverse pregnancy outcome. Seven hundred and seventy-four pregnant women were enrolled in this study between February 2016 and June 2016. Multivariate logistic regression analysis was conducted to estimate the relative risk between maternal lipids and adverse pregnancy outcome. RESULTS: Compared with the control group, during the second trimester of pregnancy, BMI, TG, and Lp(a) were risk factors for gestational diabetes mellitus; middle trimester pregnancy BMI, Lp(a), and APO-B were risk factors for pre-eclampsia; second trimester BMI and TG/HDL-C were risk factors for macrosomia; age and Lp(a) were uterine atony postpartum hemorrhage risk factors, while APO-AI was a protective factor of uterine inertia and postpartum hemorrhage; second trimester BMI, TCH, Lp(a), and TG/HDL-C were risk factors for fetal distress, while parity was a protective factor against fetal distress. CONCLUSION: Abnormal blood lipid levels in pregnancy are significantly associated with GDM, pre-eclampsia, and other adverse pregnancy outcomes.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development. AIM: To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients. METHODS: The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression. RESULTS: Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05). CONCLUSION: D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.

A Novel U-Shaped Association Between Serum Magnesium on Admission and 28-Day In-hospital All-Cause Mortality in the Pediatric Intensive Care Unit.

Objective: Our purpose is to evaluate whether serum magnesium when entering the ICU is related to 28-day in-hospital all-cause mortality in the pediatric ICU. Methods: We used the PIC database to conduct a retrospective analysis to investigate the first-time serum magnesium levels of 10,033 critically ill children admitted to the pediatric ICU, and analyzed association between serum magnesium and all-cause mortality. Smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between serum magnesium and all-cause mortality. The shape of the curve was used to describe the relationship between magnesium and 28-day in-hospital mortality. Results: There is a non-linear relationship between serum magnesium and 28-day in-hospital all-cause mortality. The U-type relationship between serum magnesium and all-cause mortality was observed. The optimal range of serum magnesium with the lowest risk of mortality was 0.74-0.93 mmol/L. As the serum magnesium level reaches the turning point (0.74 mmol/L), the risk of death decreases by 60% for every 0.1 mmol/L increase in serum magnesium; when the serum magnesium level exceeds 0.93, an increase of 0.1 mmol/L increases the risk of death by 38 %. Conclusion: Serum magnesium has a U-shaped relationship with 28-day in-hospital all-cause mortality. Both low and high serum magnesium can increase the risk of death. The best serum magnesium range when the risk of death is the lowest is 0.74-0.93 mmol/L.

Is serum vitamin D deficiency before gestational 20 weeks a risk factor for preeclampsia?

OBJECTIVE: Our aim was to assess whether serum vitamin D deficiency before gestational 20 weeks was associated with an increased risk of preeclampsia. METHODS: We investigated the serum levels of 25(OH)D before gestational 20 weeks, and analyzed associations between the 25(OH)D and the risk of preeclampsia. 7976 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Adjusted smoothing spline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and preeclampsia. RESULTS: After fully adjusting the confounding factors, serum vitamin D is a protective factor in preeclampsia (OR = 0.85, P = 0.04). Compared with adequate vitamin D, vitamin D deficiency (OR = 1.55, P = 0.031), deficiency (OR = 1.50, P = 0.049) and severe deficiency (OR = 2.6, P = 0.005) are independent of preeclampsia in pregnant women Risk factors. CONCLUSION: Vitamin D deficiency before gestational 20 weeks is a risk factor for preeclampsia.

Development and validation of a nomogram for the early prediction of preeclampsia in pregnant Chinese women.

To make early predictions of preeclampsia before diagnosis, we developed and validated a new nomogram for the early prediction of preeclampsia in pregnant Chinese women. A stepwise regression model was used for feature selection. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. The signature, which consisted of 11 selected features, was associated with preeclampsia status (P < 0.1) for the development dataset. Predictors contained in the individualized prediction nomogram included BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator levels. The model showed good discrimination, with an area under the ROC curve of 0.8563 (95% CI: 0.8364-0.8761) and good calibration. The nomogram still had good discrimination and good calibration when applied to the validation dataset (area under ROC curve of 0.8324, 95% CI: 0.7873-0.8775). Decision curve analysis demonstrated that the nomogram was clinically useful. The nomogram presented in this study incorporates BMI, blood pressure, uterine artery ultrasound parameters, and serological indicators and can be conveniently used to facilitate the individualized prediction of preeclampsia.

Sufficience serum vitamin D before 20 weeks of pregnancy reduces the risk of gestational diabetes mellitus.

OBJECTIVE: Our aim was to evaluate the relationship between serum vitamin D levels before 20 weeks of pregnancy and the risk of gestational diabetes mellitus. METHODS: This study is a retrospective study. We analyzed the relationship between serum 25 (OH) D level before 20 weeks of pregnancy (first antenatal examination) and the risk of gestational diabetes mellitus. Age, parity and pre-pregnancy body mass index were used as confounding factors. 8468 pregnant women were enrolled in this study between January 2018 and March 2020 at the Obstetrics and Gynecology Hospital of Fudan University. Adjusted smoothing splinespline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and gestational diabetes mellitus. RESULTS: After fully adjusting the confounding factors, serum vitamin D is a protective factor in gestational diabetes mellitus (OR = 0.90). Compared with vitamin D deficiency, vitamin D insufficiency (OR = 0.78), sufficience (OR = 0.82) are a protective factor for gestational diabetes mellitus. CONCLUSION: Sufficience vitamin D before 20 weeks of pregnancy is a protective factor for gestational diabetes mellitus. Vitamin D > 20 ng/mL can reduce the risk of GDM, which is not much different from the effect of > 30 ng/mL. The protective effect of vitamin D is more significant in obese pregnant women.

Serum markers in quadruple screening associated with adverse pregnancy outcomes: A case-control study in China.

BACKGROUND: We assessed whether the results of quadruple screening during pregnancy are associated with an increased risk of adverse pregnancy outcomes. METHODS: We measured serum marker concentrations using quadruple screening in the second trimester of pregnancy and analyzed the relationship between adverse perinatal outcomes and serum markers in 12,124 pregnant women. A multivariate logistic regression analysis was used to evaluate the relative risk of quadruple screening and adverse pregnancy outcomes. RESULTS: Compared with the control group, increased concentrations of alpha-fetoprotein (AFP) and inhibin A were risk factors for preeclampsia and preterm delivery; low concentrations of unconjugated estriol and high inhibin A were risk factors for pregnancy hypertension; an increased concentration of human chorionic gonadotropin (hCG) was a risk factor for gestational diabetes mellitus; high AFP, low hCG, and high inhibin A were risk factors for low birth weight; and low AFP and high hCG were risk factors for macrosomia. CONCLUSIONS: Quadruple screening in the second trimester of pregnancy can provide early warning signs for maternal and fetal adverse pregnancy outcomes.

Are serum levels of inhibin A in second trimester predictors of adverse pregnancy outcome?

OBJECTIVE: During pregnancy, inhibin A is mainly derived from the placenta and regulates the implantation and differentiation of embryos. Our aim was to assess whether second trimester serum inhibin A was associated with an increased risk of adverse pregnancy outcomes. METHODS: We investigated the serum levels of Inhibin A during the second trimester in pregnancy, and analyzed associations between the Inhibin A and the risk of adverse pregnancy outcome. 12,124 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Multivariate logistic regression analysis was conducted to estimate the relative risk between Inhibin A and adverse pregnancy outcome. RESULTS: Compared with the group without adverse pregnancy outcome, during the second trimester of pregnancy, age and Inhibin A were risk factors for pre-eclampsia, gestational diabetes mellitus and preterm delivery; Inhibin A was risk factors for low birth weight. Gravidity and Inhibin A were risk factors for macrosomia; while parity was a protective factor against pre-eclampsia, gestational hypertension and low birth weight. CONCLUSION: Elevated Inhibin A levels in pregnancy are significantly associated with pre-eclampsia, GDM, macrosomia, low birth weight and preterm delivery.

Threshold value of anti-Mullerian hormone for the diagnosis of polycystic ovary syndrome in Chinese women.

OBJECTIVE: We intended to establish the threshold for anti-Mullerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) in China. METHODS: A total of 771 women (653 with PCOS and 118 healthy controls) were enrolled. The serum AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), FSH/LH, prolactin, estradiol, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), 17α-OH progesterone (17α-OHP), fasting insulin (INS), fasting glucose, free androgen index (FAI%) and homeostasis model assessment for insulin resistance (HOMA-IR) index were analyzed, and the diagnostic utility of AMH, LH/FSH, T and INS was established using receiver operator characteristic (ROC) curves. With AMH, LH/FSH, T and INS as independent variables, a logistic regression model was established, and the ROC curve for combined detection was fitted with the probability value of the model. RESULTS: The serum level of FSH, LH, LH/FSH, AMH, FAI%, 17α-OHP, fasting INS, T, SHBG, DHEA-S and HOMA-IR were altered in the PCOS patients. The best compromise between sensitivity and specificity was found at an AMH cut-off level of 8.16 ng/ml and 5.89 ng/ml for the age groups 20-29 and 30-39 years, with the corresponding area under the curve being 0.846 and 0.865 respectively. The area under the ROC curve for combined detection was 0.951, which was significantly greater than that of each index. Finally, the concentration of AMH was associated with FSH, LH, LH/FSH, T, and ovarian volume in PCOS patients. CONCLUSION: The optimal AMH diagnostic threshold for PCOS was 8.16 ng/ml (20-29 years) and 5.89 ng/ml (30-39 years) in the Chinese population of this study. Moreover, serum AMH, LH/FSH, T and INS could be used in combination to improve the diagnostic specificity and sensitivity for the detection of PCOS.

Comparability of the effect of storage time and temperature on serum anti-Müllerian hormone measurement between original and modified enzyme-linked immunosorbent assay.

OBJECTIVE: To explore the effect of modified enzyme-linked immunosorbent assay on the AMH results is increased or decreased, and to investigate the effect of storage time and temperature on AMH measurements with and without sample premixing assay buffer using the Kangrun ELISA method. METHOD: Serum AMH concentration were measured by ELISA, consistency between two kits, and comparability between original and the modified assay under different stored conditions were analyzed by Passing-Bablok regression analysis and Bland-Altman bias evaluation. RESULT: There was a strong consistency between AMH concentrations measured in Kangrun ELISA and Ansh Labs ultra-sensitive AMH ELISA. Pre-mixing serum specimens with assay buffer gave consistent results compared with original assay. Modified protocol can reduce the amplitude of increase affected by sample aged and give the most consistent results regardless of storage conditions. CONCLUSION: Pre-mixing protocol did not influence the results of fresh serum or frozen serum incubation <3days at 4°C and -80°C, but when specimens detected after collection and stored in other storage conditions, should be pre-mixed with assay buffer to insure its accuracy.

Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy.

OBJECTIVES: IL-35 is a novel inhibitory cytokine. In this study, we investigate the serum levels of inhibitory cytokines IL-35, IL-10 and TGF-ß in both normal pregnancies and non-pregnant females, and whether IL-35 is associated with the pathogenesis of recurrent spontaneous abortion. We also try to elucidate the relationships of IL-35 with estrogen and alpha-fetoprotein (AFP). METHODS: The levels of IL-35, IL-10, TGF-ß, estradiol (E2), unconjugated estriol (uE3) and AFP were analyzed in 120 normal pregnancies, 40 women suffering recurrent spontaneous abortion, 40 postpartum healthy women and 40 non-pregnant women by enzyme-linked immunosorbent assay (ELISA). The correlations between inhibitory cytokines, estrogen and AFP were assessed with the Spearman rank correlation coefficient. RESULTS: Data are expressed as median and percentiles (Q1, Q3).The level of serum IL-35 in normal pregnancies was significantly higher than that in non-pregnant women [333.6 (59.32, 1391) pg/mL vs. 123.9 (8.763, 471.7) pg/mL; P < 0.001]. A significantly higher level of TGF-ß was observed in the first trimester only as compared to non-pregnant women [473.4 (398.0, 580.5) pg/mL vs. 379.7 (311.0, 441.3) pg/mL, P < 0.01]. The difference in serum IL-10 level between pregnant women and non-pregnant women was not significant [8.602 (5.854, 12.89) pg/mL vs. 9.339 (5.691, 12.07) pg/mL; P > 0.05]. The level of serum IL-35 in recurrent spontaneous abortion was significantly lower than that in normal early pregnancy [220.4 (4.951, 702.0) pg/mL vs. 386.5 (64.37, 1355) pg/mL; P < 0.05]. The higher IL-35 level in first trimester pregnant women correlated with E2 (r = 0.3062, P < 0.01) and AFP (r = 0.3179, P < 0.01). CONCLUSION: Serum levels of IL-35 increased in normal pregnancy and decreased in recurrent spontaneous abortion. Increased IL-35 correlated with estrogen and AFP levels in early pregnancy. IL-35 is becoming recognized as an active player in the maintenance of a successful pregnancy, but this is not the case for IL-10 or TGF-ß.

Vitamin D deficiency contributes to the reduction and impaired function of naïve CD45RA⁺ regulatory T cell in chronic heart failure.

The effect of vitamin D pertinent to cardiovascular health on the heart itself is considered to shift toward an anti-inflammatory response in chronic heart failure (CHF); however, its underlying mechanism is not completely understood. In this study, we demonstrated that plasma 25(OH)D level, negatively associated with NT-ProBNP, correlated with the decreased Treg in CHF compared to the patients with other cardiovascular diseases and healthy and older donors. Naïve Treg cell (CD4(+)CD45RA(+)Foxp3(lo)T) subset, rather than whole Treg cells, contributes to the reduction of Treg in CHF. 1,25(OH)2D treatment maintained partial expression of CD45RA on CD4(+)T cell after αCD3/CD28 monoclonal antibodies activation and ameliorated the impaired CD4(+)CD45RA(+)T cell function from CHF patients through upregulating Foxp3 expression and IL-10 secretion in vitro. Low level of vitamin D receptor (VDR) was detected in CD4(+)CD45RA(+)T cell of CHF than control, while 1,25(OH)2D treatment increased the VDR expression to exert its immunosuppression on T cell. The results of this study might provide tangible evidence to our knowledge of the impact of vitamin D supplementation on naïve Tregs, which may offer new means of preventing and treating CHF.