Causal relationship between iron status and preeclampsia-eclampsia: a Mendelian randomization analysis.

BACKGROUND: Preeclampsia/eclampsia is a severe pregnancy-related disorder associated with hypertension and organ damage. While observational studies have suggested a link between maternal iron status and preeclampsia/eclampsia, the causal relationship remains unclear. The aim of this study was to investigate the genetic causality between iron status and preeclampsia/eclampsia using large-scale genome-wide association study (GWAS) summary data and Mendelian randomization (MR) analysis. METHODS: Summary data for the GWAS on preeclampsia/eclampsia and genetic markers related to iron status were obtained from the FinnGen Consortium and the IEU genetic databases. The "TwoSampleMR" software package in R was employed to test the genetic causality between these markers and preeclampsia/eclampsia. The inverse variance weighted (IVW) method was primarily used for MR analysis. Heterogeneity, horizontal pleiotropy, and potential outliers were evaluated for the MR analysis results. RESULTS: The random-effects IVW results showed that ferritin (OR = 1.11, 95% CI: .89-1.38, p = .341), serum iron (OR = .90, 95% CI: .75-1.09, p = .275), TIBC (OR = .98, 95% CI: .89-1.07, p = .613), and TSAT (OR = .94, 95% CI: .83-1.07, p = .354) have no genetic causal relationship with preeclampsia/eclampsia. There was no evidence of heterogeneity, horizontal pleiotropy, or possible outliers in our MR analysis (p > .05). CONCLUSIONS: Our study did not detect a genetic causal relationship between iron status and preeclampsia/eclampsia. Nonetheless, this does not rule out a relationship between the two at other mechanistic levels.

Associations between velamentous or marginal cord insertion and risk of adverse perinatal outcomes in twin pregnancies: a retrospective cohort study.

BACKGROUND: Velamentous cord insertion (VCI) and marginal cord insertion (MCI) are well-known risk factors for adverse perinatal outcomes in singleton pregnancies. However, the potential links between VCI or MCI and perinatal outcomes in twin pregnancies have yet to be systematically evaluated. This study aimed to investigate the relationships between VCI or MCI and perinatal outcomes in twin pregnancies. METHODS: This retrospective single-center cohort study included women with twin pregnancies who gave birth in a tertiary hospital in Southwest, China between January 2017 and December 2022. VCI and MCI were identified by abdominal ultrasound and confirmed after placental delivery. Logistic regression, multinomial logit regression and generalized estimation equation models were used to evaluate the association between VCI or MCI and perinatal outcomes. RESULTS: A total of 3682 twin pregnancies were included, including 100 (2.7%) pregnancies with VCI and 149 (4.0%) pregnancies with MCI. Compared to pregnancies with normal cord insertion, both monochorionic and dichorionic pregnancies with VCI were associated with an increased risk of preterm delivery 32-34 weeks (aRRR 2.94, 95% CI 1.03-8.39; aRRR 2.55, 95% CI 1.19-5.46, respectively), while pregnancies with MCI were not associated with preterm delivery. VCI was associated with a higher incidence of placental previa (aOR 6.36, 95% CI 1.92-21.04) in monochorionic pregnancies and placental accreta (aOR 1.85, 95% CI 1.06-3.23) in dichorionic pregnancies. MCI was associated with an increased risk of preeclampsia (aOR 3.07, 95% CI 1.49-6.32), intertwin birthweight discordance ≥ 20% (aOR 2.40, 95% CI 1.08-5.60) and selective fetal growth restriction (aOR 2.46, 95% CI 1.08-5.60) in monochorionic pregnancies and small-for-gestational age neonates (aOR 1.97, 95% CI 1.24-3.14) in dichorionic pregnancies. CONCLUSIONS: VCI was associated with an increased risk of preterm delivery in twin pregnancies irrespective of chorionicity, whereas MCI was associated with an increased preeclampsia risk, significant intertwin birthweight discordance in monochorionic pregnancies and small-for-gestational age neonates in dichorionic pregnancies.

Development and validation of a prediction model on spontaneous preterm birth in twin pregnancy: a retrospective cohort study.

BACKGROUND: This study was conducted to develop and validate an individualized prediction model for spontaneous preterm birth (sPTB) in twin pregnancies. METHODS: This a retrospective cohort study included 3845 patients who gave birth at the Chongqing Maternal and Child Health Hospital from January 2017 to December 2022. Both univariable and multivariable logistic regression analyses were performed to find factors associated with sPTB. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). Model performance was estimated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 1313 and 564 cases were included in the training and testing sets, respectively. In the training set, univariate and multivariate logistic regression analysis indicated that age ≥ 35 years (OR, 2.28; 95% CI 1.67-3.13), pre-pregnancy underweight (OR, 2.36; 95% CI 1.60-3.47), pre-pregnancy overweight (OR, 1.67; 95% CI 1.09-2.56), and obesity (OR, 10.45; 95% CI, 3.91-27.87), nulliparity (OR, 0.58; 95% CI 0.41-0.82), pre-pregnancy diabetes (OR, 5.81; 95% CI 3.24-10.39), pre-pregnancy hypertension (OR, 2.79; 95% CI 1.44-5.41), and cervical incompetence (OR, 5.12; 95% CI 3.08-8.48) are independent risk factors for sPTB in twin pregnancies. The AUC of the training and validation set was 0.71 (95% CI 0.68-0.74) and 0.68 (95% CI 0.64-0.73), respectively. And then we integrated those risk factors to construct the nomogram. CONCLUSIONS: The nomogram developed for predicting the risk of sPTB in pregnant women with twins demonstrated good performance. The prediction nomogram serves as a practical tool by including all necessary predictors that are readily accessible to practitioners.

Investigation of optimal gestational weight gain for twin pregnancy in Southwest China: a retrospective study.

There is a lack of data on gestational weight gain (GWG) in twin pregnancies. We divided all the participants into two subgroups: the optimal outcome subgroup and the adverse outcome subgroup. They were also stratified according to prepregnancy body mass index (BMI): underweight (< 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight (24-27.9 kg/m2), and obese (≥ 28 kg/m2). We used 2 steps to confirm the optimal range of GWG. The first step was proposing the optimal range of GWG using a statistical-based method (the interquartile range of GWG in the optimal outcome subgroup). The second step was confirming the proposed optimal range of GWG via compared the incidence of pregnancy complications in groups below or above the optimal GWG and analyzed the relationship between weekly GWG and pregnancy complications to validated the rationality of optimal weekly GWG through logistic regression. The optimal GWG calculated in our study was lower than that recommended by the Institute of Medicine. Except for the obese group, in the other 3 BMI groups, the overall disease incidence within the recommendation was lower than that outside the recommendation. Insufficient weekly GWG increased the risk of gestational diabetes mellitus, premature rupture of membranes, preterm birth and fetal growth restriction. Excessive weekly GWG increased the risk of gestational hypertension and preeclampsia. The association varied with prepregnancy BMI. In conclusion, we provide preliminary Chinese GWG optimal range which derived from twin-pregnant women with optimal outcomes(16-21.5 kg for underweight, 15-21.1 kg for normal weight, 13-20 kg for overweight), except for obesity, due to the limited sample size.

Measuring maternal body composition by biomedical impedance can predict risk for gestational diabetes mellitus: a retrospective study among 22,223 women.

OBJECTIVES: This study aimed to identify which element of body composition measurements taken before 17th week gestation was the strongest risk factor for gestational diabetes mellitus (GDM) in Chinese pregnant women. DESIGN AND SETTING: A retrospective study was performed using data retrieved from the Electronic Medical Record database of Chongqing Health Center for Women and Children (China) from January 2014 to December 2015. PARTICIPANTS: A total of 22,223 women were included with singleton pregnancies and no preexisting diabetes who underwent bioelectrical impedance analysis (BIA) before 17 gestational weeks and 75-g OGTT at 24-28 gestational weeks. RESULTS: The prevalence of GDM from 2014 to 2015 was 27.13% (IADPSG). All indicators of BIA (total body water, fat mass, fat-free mass, percent body fat, muscle mass, visceral fat levels, proteins, bone minerals, basal metabolic rate, lean trunk mass), age, weight and body mass index (BMI) were risk factors that significantly increased the occurrence of GDM (p < .001 for all). Women older than 30 years or with a BMI more than 23, had a significantly higher GDM prevalence (34.89% and 34.77%). After adjusted covariates, visceral fat levels at the third quartile, the ORs of GDM were 1.142 (95% CI 1.032-1.263) in model I and 1.419 (95% CI 1.274-1.581) in model II used the first quartile as reference (p < .05 for both); bone minerals at the third quartile, the ORs of GDM were 1.124 (95% CI 1.020-1.238) in model I and 1.311 (95% CI 1.192-1.442) in model II (p < .05 for both). After adjusted for age, visceral fat levels and bone minerals, OR of GDM for percent body fat more than 28.77% at the third quartile was 1.334 (95% CI 1.201-1.482) in model II (p < .05 for both). CONCLUSIONS: Visceral fat levels, bone minerals and percent body fat were significantly associated with an increased risk of GDM, providing the reference ranges of visceral fat levels, bone minerals and percent body fat as predictive factors for Chinese women to estimate the risk of GDM by BIA during pregnancy.

Perinatal outcomes of twin pregnancies with preterm premature rupture of the membranes at 24-34 weeks' gestation.

To describe the perinatal outcomes of twin pregnancies with preterm premature rupture of membranes (PPROM) before 34 weeks' gestation and identify factors associated with discharge without severe or moderate-severe neonatal morbidity. This study was conducted as a retrospective analysis of twin pregnancies with PPROM occurring at 24 0/7 to 33 6/7 weeks' gestation. Perinatal outcomes were assessed by gestational age (GA) at PPROM and compared between PPROM and non PPROM twins. Factors associated with discharge without severe or moderate-severe neonatal morbidity were identified using logistic regression analysis. Of the 180 pregnancies (360 foetuses), only 17 (9.4%) women remained pregnant 7 days after PPROM. There were 10 (2.8%) cases of prenatal or neonatal death; 303 (84.2%) and 177 (49.2%) neonates were discharged without severe or moderate-severe morbidity, respectively. As GA at PPROM increased, the adverse obstetric and neonatal outcomes decreased, especially after 32 weeks. There was no significant difference in general neonatal outcomes between PPROM and non PPROM twins. The GA at PPROM and latency period were both significantly associated with discharge without severe or moderate-severe neonatal morbidity. Pregnancy complications and 5-min Apgar score < 7 increased severe neonatal morbidity. As GA at PPROM increased, the risk of adverse perinatal outcomes decreased. GA at PPROM and latency period were significantly associated with discharge without severe or moderate-severe neonatal morbidity.

High-glucose/high-cholesterol diet in zebrafish evokes diabetic and affective pathogenesis: The role of peripheral and central inflammation, microglia and apoptosis.

Neuroinflammation and metabolic deficits contribute to the etiology of human affective disorders, such as anxiety and depression. The zebrafish (Danio rerio) has recently emerged as a powerful new model organism in CNS disease modeling. Here, we exposed zebrafish to 2% glucose and 10% cholesterol for 19 days to experimentally induce type 2 diabetes (DM) and to assess stress responses, microglia, inflammation and apoptosis. We analyzed zebrafish anxiety-like behavior in the novel tank and light-dark box (Days 15-16) tests, as well as examined their biochemical and genomic biomarkers (Day 19). Confirming DM-like state in zebrafish, we found higher whole-body glucose, triglyceride, total cholesterol, low-density lipoprotein levels and glucagon mRNA expression, and lower high-density lipoprotein levels. DM zebrafish also showed anxiety-like behavior, elevated whole-body cortisol and cytokines IFN-γ and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor, CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6 and TNF-α (but not IL-1ß or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocytal biomarker), neurotrophin BDNF, its receptors p75 and TrkB, as well as apoptotic Bax and Caspase-3 (but not BCl-2) genes. Collectively, this supports the overlapping nature of DM-related affective pathogenesis and emphasizes the role of peripheral and central inflammation and apoptosis in DM-related affective and neuroendocrine deficits in zebrafish.