Inhibition of the endoplasmic reticulum stress-associated IRE-1 pathway alleviates preterm birth.

BACKGROUND: Premature birth (PTB) remains a major global health concern due to its association with neonatal morbidity and mortality. The unfolded protein response (UPR) within the endoplasmic reticulum (ER) is tightly regulated by Inositol-requiring enzyme type 1 (IRE-1), a pivotal cellular modulator. This study seeks to elucidate the role of the ER stress (ERS)-related IRE-1 pathway in PTB. METHODS: Human placental trophoblast cells HTR8/Svneo were exposed to the ER-stress inducer tunicamycin (TM). The expression of IRE-1 and ERS-associated proteins ATF6, GRP78, and XBP-1 was assessed in placental tissues and TM-treated cells. Cellular viability, migration, invasion, and apoptosis were evaluated through a series of experimental assays. Additionally, various methods were employed to assess and verify the activation of autophagy, using the autophagy marker, microtubule-associated protein 1A/1B-light chain 3 (LC3). Additionally, TUDCA (an ERS inhibitor) was used to assess its potential to counteract the TM-induced cell effects. RESULTS: Elevated levels of ATF6, GRP78, and XBP-1 were observed in PTB tissues and cells. TM treatment substantially reduced cell viability, migration, and invasion while promoting apoptosis. Treatment with TUDCA (an ERS inhibitor) counteracted the effects of TM on the cells. Furthermore, we identified an overexpression of IRE-1 in PTB tissues and cells and its knockdown enhanced cell viability, migration, and invasion while suppressed apoptosis and autophagy under TM stimulation. Notably, IRE-1 was found to modulate the activity of the IRE-1/XBP1/CHOP signaling pathway in TM-treated cells. CONCLUSION: The upregulation of IRE-1 in PTB placental tissues is implicated in the pathogenesis of PTB. Importantly, inhibiting the ERS-associated IRE-1/XBP1/CHOP pathway may be a good strategy in mitigating PTB.

Nox2 inhibition reduces trophoblast ferroptosis in preeclampsia via the STAT3/GPX4 pathway.

AIMS: Ferroptosis, a novel mode of cell death characterized by lipid peroxidation and oxidative stress, plays an important role in the pathogenesis of preeclampsia (PE). The aim of this study is to determine the role of Nox2 in the ferroptosis of trophoblast cells, along with the underlying mechanisms. METHODS: The mRNA and protein levels of Nox2, STAT3, and GPX4 in placental tissues and trophoblast cells were respectively detected by qRT-PCR and western blot analysis. CCK8, transwell invasion and tube formation assays were used to evaluate the function of trophoblast cells. Ferroptosis was evaluated using flow cytometry and the lipid peroxidation assay. Glycolysis and mitochondrial respiration were investigated by detecting the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) using Seahorse extracellular flux technology. The t-test or one-way ANOVA was used for statistical analysis. KEY FINDINGS: Nox2 was up-regulated while STAT3 and GPX4 were down-regulated in PE placental tissues. Nox2 knockdown inhibited ferroptosis in trophoblast cells, which was shown by enhanced proliferation and invasion, decreased ROS and lipid peroxide levels, and reduced glycolysis and mitochondrial dysfunction. Nox2 negatively correlated with MVD in PE placentas, and Nox2 knockdown restored ferroptosis-inhibited tube formation. Nox2 could interact with STAT3. Inhibiting Nox2 restored ferroptosis-induced alterations in the mRNA and protein levels of STAT3 and GPX4. SIGNIFICANCE: Nox2 may trigger ferroptosis through the STAT3/GPX4 pathway, subsequently leading to regulation of mitochondrial respiration, transition of glycolysis, and inhibition of placental angiogenesis. Therefore, targeted inhibition of Nox2 is expected to become a new therapeutic target for PE.

Gestational weight trajectory and risk of adverse pregnancy outcomes among women with gestational diabetes mellitus: A retrospective cohort study.

The aim of this study was to explore gestational weight gain (GWG) trajectories and their associations with adverse pregnancy outcomes. A retrospective cohort study including 11,064 women with gestational diabetes mellitus (GDM) was conducted between 2015 and 2019 in China. The latent class trajectory model was used to identify GWG trajectories, and logistic regression was performed to examine odds ratio (OR) of pregnancy outcomes. Three trajectories of GWG were identified in these 11,604 women with GDM. Trajectory 1: 64.02% of women had sustained moderate GWG throughout pregnancy; Trajectory 2: 17.75% of women showed a high initial GWG but followed by a low GWG from the third trimester until delivery; Trajectory 3: 18.23% had low initial GWG but followed by drastic GWG from the second trimester until delivery. Compared with pregnant women with Trajectory 1, women with Trajectory 2 had a higher risk of large for gestational age (adjusted odds ratio [AOR]: 1.29, 95% confidence interval [CI]: 1.12-1.48) but at a lower risk of having hypertensive disorders of pregnancy (AOR: 0.76, 95% CI: 0.57-0.96). Women in Trajectory 3 were more likely to develop small for gestational age (AOR: 2.12, 95% CI: 1.62-2.78), low birthweight (AOR: 1.49, 95% CI: 1.07-2.08), preterm birth (AOR: 1.28, 95% CI: 1.05-1.63), caesarean section (AOR: 1.26, 95% CI: 1.112-1.42) and hypertensive disorders of pregnancy (AOR: 2.24, 95% CI: 1.82-2.76). The association of GWG trajectory with adverse pregnancy outcomes differs across prepregnancy body mass index and GWG categories. Women with a slow initial GWG but followed by drastic GWG had higher risks of adverse pregnancy outcomes. Early clinical recognition of poor GWG trajectory will contribute to early intervention in high-risk groups to minimise adverse outcomes.

Analysis of the clinical diagnosis and treatment of fetal meconium peritonitis.

BACKGROUND: The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis (FMP), as well as the diagnostic efficacy of ultrasound for FMP. METHODS: The clinical data of 41 infants and pregnant women diagnosed with meconium peritonitis (MP) and treated at the Fujian Maternal and Child Health Hospital from January 2013 to January 2020 were analyzed retrospectively. Clinical data, imaging data, complications, treatment strategies, pregnancy outcomes, neonatal prognoses, and follow-up outcomes were all analyzed. RESULTS: The MP prenatal diagnosis rate was 56.1% (23/41), the neonatal surgery rate was 53.7% (22/41), and the survival rate was 85.4% (35/41). Intraperitoneal calcification (23 pregnant women, 56.1%), intestinal dilatation (13 pregnant women, 31.7%), peritoneal effusion (22 pregnant women, 53.7%), intraperitoneal pseudocyst (7 pregnant women, 17.1%), and polyhydramnios were diagnosed via prenatal ultrasound (18 pregnant women, 43.9%). Twenty-two pregnant women were assigned to the surgical treatment (operation) group, while 18 were assigned to the conservative treatment group. In the operation group, there were 9 cases of ileal atresia (40.9%), 7 cases of jejunal atresia (31.8%), 2 cases of atresia at the jejunum-ileum junction (9.1%), 2 cases of ileal perforation (9.1%), 1 case of ileal necrosis (4.5%), and 1 case of adhesive obstruction (4.5%). There was no statistically significant difference (p > .05) in the occurrence of various prenatal ultrasound findings by etiology. CONCLUSION: Multiple prenatal ultrasound markers have been identified for MP. To improve the efficacy of newborn treatment for FMP and reduce neonatal mortality, dynamic monitoring of ultrasound image alterations and strengthened integrated perinatal management are necessary.

Association of maternal body mass index change with risk of large for gestational age among pregnant women with and without gestational diabetes mellitus: a retrospective cohort study.

OBJECTIVE: To investigate the associations of body mass index (BMI) change and large for gestational age (LGA) among prepregnancy normal-weight women with and without gestational diabetes mellitus (GDM). METHODS: The retrospective study including 9515 normal-weight pregnant women (1331 women with GDM and 8184 without GDM) was conducted in Fujian Maternity and Child Health Hospital in 2020. The BMI change was calculated as gestational weight gain in kilograms by maternal height in meters. The binary logistic regression, stratified analyses, restricted cubic spline models and additive interaction analysis were adopted to reveal the relationship between BMI change and LGA. RESULTS: Pregnant women with GDM had a lower level of BMI change but a higher incidence of LGA compared with those without GDM. After adjustment for covariates variables, we found that the risk of LGA was associated with the highest quartile of BMI change (OR = 1.89, 95%CI:1.27-2.8 for GDM and OR = 1.48,95%CI:1.27-1.75 for non-GDM). There were significant linear relationships of BMI change and LGA with the inflection point of 5.096 and 5.401 kg/m2 in GDM and non-GDM groups. Significant additive interaction was observed between parity and BMI change level concerning LGA. A significant difference in BMI change and gestational weight gain (GWG) for LGA prediction was detected. CONCLUSION: Higher BMI changes were significantly associated with a higher risk of LGA in pregnant women with or without GDM in a linear dose-response relationship, with the threshold around 5.096 and 5.401 kg/m2, respectively. These suggested that BMI changes may be a useful predictor for the incidence of LGA in singleton pregnant women.

Associations of elevated glucose levels at each time point during OGTT with fetal congenital heart diseases: a cohort study of 72,236 births.

BACKGROUND: It remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring. METHODS: We conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD. RESULTS: A total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses. CONCLUSION: Elevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD.

Application of Team-Based Flipped Classroom and Traditional Learning on the Antenatal Education Center Course.

Background: The goal is to evaluate the effects of a flipped class strategy on knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes in primiparas undergoing antenatal education. Methods: A random sampling method was adopted. A total of 600 primiparas who were diagnosed with early pregnancy in a first-class hospital in southeast China and received continuous prenatal health education from May to July 2020 were selected as the research subjects. In order to make the baseline of the two groups of primipara comparable, we divided the two groups in the antenatal education centre according to the odd-even number of the lesson card number. The odd-numbered group was the experimental group, who used the prenatal health education model based on blended learning; the even-numbered group was the control group, who used the traditional mode of prenatal health education. The two groups were compared on the following outcomes: knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes. Results: Compared with traditional learning, the blended learning approach can effectively controlled the gestational weight gain (GWG), alleviated the anxiety and depression during pregnancy, improved the natural delivery rate of the primipara, shortened the delivery process and reduced the risk of gestational diabetes mellitus (GDM), the difference was statistically significant (all P<0.05). Conclusion: Blended learning may be an effective strategy because of its validity and practicality in antenatal education.

LncRNA PSMA3-AS1 promotes preterm delivery by inducing ferroptosis via miR-224-3p/Nrf2 axis.

Long non-coding RNAs (lncRNAs) have a vital potential in premature delivery. This research was intended to explore PSMA3-AS1's role in premature delivery as well as its possible molecular mechanism. We enrolled 100 premature delivery patients and 100 term patients. Fetal membranes were collected. RT-qPCR was adopted for evaluating PSMA3-AS1, miRNA-224-3p, along with Nrf2 expression. Cell function experiments were implemented to clarify PSMA3-AS1 functions in human trophoblast HTR-8/SVneo cells. Rescue together with mechanistic experiments were implemented for assessing the regulatory function and interaction between miR-224-3p and PSMA3-AS1 or Nrf2 axis in human trophoblast cells. The results uncovered that PSMA3-AS1 level presented downregulation in the fetal membrane tissues and human trophoblast cells. Overexpressed PSMA3-AS1 enhanced cell proliferation but suppressed ferroptosis in human trophoblast cells. Besides, PSMA3-AS1 elevation also attenuated the LPS-induced inflammatory response and restored the LPS-induced upregulation of 20α-HSD and downregulation of progesterone (P4). Mechanistically, miR-224-3p could bind to PSMA3-AS1 and present upregulation in fetal membranes and human trophoblast cells. Notably, overexpressed miR-224-3p offset the influences of PSMA3-AS1 on human trophoblast cell proliferation and ferroptosis. Furthermore, Nrf2 was targeted by miR-224-3p. Downregulated Nrf2 offset the influences of the miR-224-3p inhibitor and induced HTR-8/SVneo dysfunction. Additionally, Nrf2 transcriptionally activated PSMA3-AS1 and GPX4. In conclusion, PSMA3-AS1 expression is low during premature delivery and overexpressing PSMA3-AS1 promotes proliferation and suppresses ferroptosis of human trophoblast cells by interacting with miR-224-3p to downregulate Nrf2. Therefore, enhancing PSMA3-AS1 expression may be a promising therapeutic strategy to prevent premature delivery.

Predicting risk of postpartum hemorrhage associated with vaginal delivery of twins: A retrospective study.

Many studies have only focused on the risk factors for postpartum hemorrhage (PPH) in singleton vaginal deliveries and twin cesarean deliveries. We analyzed the factors of influencing PPH occurrence in twin vaginal deliveries and developed a nomogram for clinical application. This retrospective study included 274 pregnant women with twin pregnancies who were hospitalized for delivery from January 2014 to December 2018. The patients opted for vaginal delivery and experienced spontaneous labor. Univariate analysis of PPH risk factors was performed. Multivariate analysis was performed using the least absolute shrinkage and selection operator (LASSO) to obtain relevant factors and build a prediction model, which was presented as a nomogram. The model was internally validated by bootstrap self-sampling method. Model accuracy was evaluated with the concordance index (C-index). There were 36 (13.14%) and 238 (86.9%) patients in the PPH and no PPH groups, respectively. Univariate analysis identified twin chorionicity, hypertensive disorders complicating pregnancy (HDCP), anemia in pregnancy, delivery mode of the second twin, oxytocin use during labor, postpartum curettage, cervical laceration, intrapartum fever, fibrinogen degradation products (FDP), and platelet count (PLT) as significant PPH factors. On multivariate analysis, HDCP, anemia in pregnancy, intrapartum fever, oxytocin use during labor, fetal distress, PLT, direct bilirubin, and FDP were noted as significant PPH factors and were included in the prediction model. A C-index of 0.816 was noted after internal validation, and the calibration curve showed good consistency. We developed a model to predict PPH risk in the vaginal delivery of twin pregnancies and visualized it with a nomogram that can be applied clinically to assess PPH risk and aid PPH prevention.

Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage.

PURPOSE: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. METHODS: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. RESULTS: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). DISCUSSION: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

The application of rapid response team in category 1 emergency caesarean section teaching for OBGYN residents in the delivery room.

Category 1 cesarean section (CS) can be a life-saving procedure when there is immediate threat to the life of the woman or fetus. However, category 1 CS is a challenge for obstetrics and gynecology residents, and it is necessary to establish an effective and straightforward teaching strategy. This study aimed to evaluate the efficiency of rapid response team (RRT) on category 1 CS teaching for obstetrics and gynecology residents in the delivery room. A total of 142 residents who underwent standardized residency training programs in the delivery room were divided into a RRT teaching group and a traditional response (TR) teaching group. In the RRT teaching group, Category 1 emergency CS teaching was started and explored by rapid response team. The training included both theoretical and practical components. After the training, decision-to-delivery interval (DDI), neonatal Apgar score, operation time and rate of postpartum hemorrhage were compared. A questionnaire on the subjective assessment of various aspects of the program was conducted at the end of the training period. The DDI in minutes in the RRT teaching group (n = 72) was significantly shorter than that of the TR teaching group (n = 70) (11.83 ±â€…4.16 vs 13.56 ±â€…5.47, P = .0364). The score of satisfaction from residents in the RRT teaching group was significantly higher than that of the TR group [7 (6, 9) vs 9 (7, 10), P = .0154]. Compared with the TR teaching group, more residents thought their clinical skills have been improved (94.29% vs 100%, P = .0396) and willing to recommend their training method to others (91.43% vs 100%, P = .0399) in the RRT teaching group. However, no significant differences were observed in the incidence of postpartum hemorrhage between the 2 groups. RRT teaching is beneficial in the standardized training and teaching of residents in the delivery room. It improves the DDI of category 1 emergency cesarean section and the degree of satisfaction.

Placenta-derived exosomal miR-135a-5p promotes gestational diabetes mellitus pathogenesis by activating PI3K/AKT signalling pathway via SIRT1.

Most people are aware of gestational diabetes mellitus (GDM), a dangerous pregnancy complication in which pregnant women who have never been diagnosed with diabetes develop chronic hyperglycaemia. Exosomal microRNA (miRNA) dysregulation has been shown to be a key player in the pathophysiology of GDM. In this study, we looked into how placental exosomes and their miRNAs may contribute to GDM. When compared to exosomes from healthy pregnant women, it was discovered that miR-135a-5p was elevated in placenta-derived exosomes that were isolated from the maternal peripheral plasma of GDM women. Additionally, we discovered that miR-135a-5p encouraged HTR-8/SVneo cell growth, invasion and migration. Further research revealed that miR-135a-5p activates HTR-8/SVneo cells' proliferation, invasion and migration by promoting PI3K/AKT pathway activity via Sirtuin 1 (SIRT1). The transfer of exosomal miR-135a-5p generated from the placenta could be viewed as a promising agent for targeting genes and pertinent pathways involved in GDM, according to our findings.

Increased expression levels of DLX5 inhibit the development of the nervous system.

INTRODUCTION: Preeclampsia is a hypertensive disorder of pregnancy. DLX5 plays an important role in the migration and differentiation of subglobus pallidus precursor cells. METHODS: We established a zebrafish line expressing high levels of DLX5 and investigated changes in behavior and development of the nervous system. RESULTS: The ratios of brain volume area to whole body area at 96 hpf zebrafish in the experimental group (gRNA + CasRx) were significantly lower than the WT group and the negative control group (casRx) (P < 0.01). Behavioral trajectory distances and movement speeds exhibited by the 6th day of development in zebrafish in the experimental group (gRNA + CasRx) were significantly shorter (P < 0.01) and lower (P < 0.05) than the negative control group (gRNA + CasRx), respectively. CONCLUSIONS: Data suggested that the increased expression levels of DLX5 can inhibit brain volume development and behavioral activities in zebrafish. Maybe the high expression levels of DLX5 in the pathological state of preeclampsia can inhibit the development of the nervous system in offspring.

Relationship between gestational weight gain during different phases and maternal complications or neonatal outcomes.

OBJECTIVES: Improper gestational weight gain (GWG) causes many adverse obstetrical and neonatal outcomes. This study evaluates the relationship between weight gain in different phases and maternal outcomes or neonatal outcomes. MATERIAL AND METHODS: Finally, this study recruited 2,608 women delivered at Fujian Provincial Maternity and Child Health, affiliated hospital of Fujian Medical University from December 2017 to January 2019. To evaluate the relationship between maternal outcome and neonatal outcome, the participants were divided into four groups based on their baseline BMI and weight gain in the second/third trimester of pregnancy. RESULTS: This study demonstrated that neonate weight, small-for-gestational-age infants, macrosomia, neonatal death, cesarean delivery, and GDM significantly differed across the baseline BMI, weight gain in the second and third trimester. The umbilical cord's abnormality, bulging membrane, abruptio placentae, and postpartum hemorrhage were significantly related to baseline BMI. Furthermore, gestational hypertension and pre-eclampsia/eclampsia were significantly correlated with baseline BMI and weight gain in the second trimester. The maternal and infant outcomes are different, and the GWG curves are significantly different. Finally, multivariate regression analysis showed that baseline BMI and weight gain in the second/third trimester were the independent risk factors for GDM and macrosomia. Also, baseline BMI and weight gain in the third trimester were the independent risk factors for developing gestational hypertension and pre-eclampsia/eclampsia, respectively. CONCLUSIONS: The baseline BMI and weight gain in the second/third trimester are significant with maternal outcomes and neonatal outcomes to a varying degree. Thus, maintaining appropriate baseline BMI and weight gain in different phases are essential in preventing pregnancy complications and maternal and neonatal prognosis.

Correlation between serum ferritin in early pregnancy and hypertensive disorders in pregnancy.

Objective: To explore the correlation between serum ferritin (SF) in early pregnancy and the risk of hypertensive disorders in pregnancy (HDP). Method: A retrospective cohort study was conducted on 43,421 pregnant women with singleton pregnancies who underwent antenatal checkups at Fujian Provincial Maternal and Child Health Hospital from January 2018 to December 2020. Based on pregnancy records, women were classified as non-hypertensive, having gestational hypertension, preeclampsia and preeclampsia with severe features according to the degree of the disease. General baseline data, and SF levels in the early (up to 12 gestational weeks) and late (after 28 weeks of gestation) stages of pregnancy were collected. The significance of the characteristic variables was assessed using a random forest algorithm, and the correlation between early pregnancy SF levels and the incidence of HDP was further analyzed using logistics regression adjusted for confounders. A generalized additive model (GAM) was fitted to a smoothed graph of the relationship between early pregnancy SF levels and HDP, and a threshold effect analysis was performed to find the threshold values of early pregnancy SF for iron supplementation therapy. Result: A total of 30,703 pregnant women were included. There were 1,103 women who were diagnosed with HDP. Of them, 418 had gestational hypertension, 12 had chronic hypertension without SPE, 332 - preeclampsia and 341 women had preeclampsia with severe features. Levels of SF in early and late pregnancy were significantly higher (p < 0.001) in women with HDP compared to non-hypertensive women and the difference was more pronounced in early pregnancy. The random forest algorithm showed that early pregnancy SF was more effective in predicting HDP compared to late pregnancy SF levels and was also an independent risk factor for HDP (adjusted odds ratio (AOR) = 1.07, 95% CI [1.05,1.09]) after correction for confounding factors. Early pregnancy SF >64.22 mg/l was associated with higher risk of developing hypertensive disorders. Conclusion: Risk of pregnancy-related hypertensive disorders increases with increasing early pregnancy SF levels. SF levels may therefore be used to further develop guidelines for iron supplementation therapy in pregnant women.

Involvement of oxytocin receptor deficiency in psychiatric disorders and behavioral abnormalities.

Oxytocin and its target receptor (oxytocin receptor, OXTR) exert important roles in the regulation of complex social behaviors and cognition. The oxytocin/OXTR system in the brain could activate and transduce several intracellular signaling pathways to affect neuronal functions or responses and then mediate physiological activities. The persistence and outcome of the oxytocin activity in the brain are closely linked to the regulation, state, and expression of OXTR. Increasing evidence has shown that genetic variations, epigenetic modification states, and the expression of OXTR have been implicated in psychiatric disorders characterized by social deficits, especially in autism. Among these variations and modifications, OXTR gene methylation and polymorphism have been found in many patients with psychiatric disorders and have been considered to be associated with those psychiatric disorders, behavioral abnormalities, and individual differences in response to social stimuli or others. Given the significance of these new findings, in this review, we focus on the progress of OXTR's functions, intrinsic mechanisms, and its correlations with psychiatric disorders or deficits in behaviors. We hope that this review can provide a deep insight into the study of OXTR-involved psychiatric disorders.

Interactive effects of gestational diabetes mellitus and maximum level of total bile acid in maternal serum on adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy.

OBJECTIVE: To study the combined effect of gestational diabetes mellitus (GDM) and maximum level of maternal serum total bile acid (TBA) on the incidence of adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy (ICP). METHODS: This was an observational study with 724 women with ICP. Perinatal outcomes were compared by the presence of GDM. Logistic regression was used to assess the independent and multiplicative interactions of GDM and maximum maternal serum TBA on adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Andersson to calculate relative excess risks. RESULTS: The incidence of GDM in patients with ICP was 21.55%. Maternal age, pre-pregnancy weight, parity, and gravidity were positively correlated with GDM. Hypertensive disorders of pregnancy (HDP) and fetal distress rates were higher in the GDM vs. non-GDM group. There were no significant differences in biochemical outcomes (i.e., Triglyceride (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA)) between the two groups. In terms of adverse pregnancy outcomes, GDM was only associated with maximum TBA concentration for cesarean section. No additive or pairwise interactions were detected between GDM and maximum TBA concentration and HDP, PPH, preterm delivery, LGA, SGA, and cesarean section. CONCLUSION: GDM independently contributes to adverse pregnancy outcomes among women with ICP. However, the combined effects of GDM and maximum TBA concentration on adverse pregnancy outcomes do not appear to be multiplicative or additive.

A preliminary integrated analysis of miRNA-mRNA expression profiles reveals a role of miR-146a-3p/TRAF6 in plasma from gestational diabetes mellitus patients.

OBJECTIVES: To utilize an integrative strategy to construct functional miRNA-mRNA regulatory networks by combining the reverse expression relationships between miRNAs and targets and computational predictions for gestational diabetes mellitus (GDM). MATERIAL AND METHODS: A total of three microarray or RNA-seq datasets (GSE98043, GSE19649 and GSE92772) of plasma samples comparing GDM pregnant women and healthy control pregnant women were downloaded from the GEO database. The differentially expressed genes (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) was performed. The target genes of DEmiRNAs were identified using two independent and complementary types of information: computational target predictions and expression relationships. An interaction network was constructed to identify hub genes of GDM. Another dataset (GSE92772) was used to externally verify the predictive ability of the hub genes. RESULTS: A total of 264 DEmiRNAs and 1217 DEmRNAs were identified with Hsa-miR-146a-3p ranked first of DEmiRNAs. Functions of GDM-related miRNAs were mainly enriched in the glypican pathway, proteoglycan syndecan-mediated signaling events, and syndecan-1-mediated signaling events. A total of 47 target genes, including TRAF6, were shared between the computational target predictions and DEmRNAs and were identified as target genes of hsa-miR-146a-3p. The interaction network analysis identified TRAF6, CASP8, PTPN6, and CHD3 as hub genes involved in the pathophysiological process of GDM. Next, independent external validation was performed using the GSE19649 dataset. The expression of TRAF6, CASP8 and CHD3 in eight pairs of GDM blood samples was confirmed to be higher than that in healthy pregnant women blood samples with a AUC of 0.813, 0.813, and 0.703, respectively. CONCLUSIONS: Our preliminary analysis revealed that miR-146a-3p/TRAF6 might play a central role in the pathogenesis of GDM. Three hub genes, TRAF6, CASP8, and CHD3, were identified and independently externally validated as potential GDM noninvasive serum markers for future biomarkers research.

Interactive effect of prepregnancy overweight/obesity and GDM history on prevalence of GDM in biparous women.

Background: Prepregnancy overweight/obesity (OWO) and gestational diabetes mellitus (GDM) history may increase the prevalence of GDM in parous women, but little is known about their potential combined effect on the prevalence of GDM in biparous women. Objective: This study aims to explore the interactive effect of prepregnancy overweight/obesity (OWO) and GDM history on the prevalence of GDM in biparous women. Methods: A retrospective study was conducted on 16,282 second-birth women who delivered a single neonate at ≧28 weeks of gestation twice. Logistic regression was used to assess the independent and multiplicative interactions of prepregnancy overweight/obesity (OWO) and GDM history on the risk of GDM in biparous women. Additive interactions were calculated using an Excel sheet that was made by Anderson to calculate relative excess risk. Results: A total of 14,998 participants were included in this study. Both prepregnancy OWO and GDM history were independently associated with an increased risk of GDM in biparous women (odds ratio (OR) = 19.225, 95% confidence interval (CI) = 17.106, 21.607 and OR = 6.826, 95% CI = 6.085, 7.656, respectively). The coexistence of prepregnancy OWO and GDM history was associated with GDM, with an adjusted OR of 1.754 (95% CI, 1.625, 1.909) compared to pregnant women without either condition. The additive interaction between prepregnancy OWO and GDM history was found to be not significant with regard to GDM in biparous women. Conclusions: Prepregnancy OWO and GDM history both increase the risk of GDM in biparous women and have multiplicative interactions but not additive interactions.