METTL3 mediates m6A modification of hsa_circ_0072380 to regulate the progression of gestational diabetes mellitus.

BACKGROUND: m6A modification plays a vital role in gestational diabetes mellitus (GDM) progression. However, the role of METTL3 and differential m6A-modified circRNAs in GDMstayto be investigated. METHODS: Placental tissue samples from GDM patients and normal controls (NC) were collected to measure changes in m6A modification levels. MeRIP-seq on placental tissue was performed to detect differential m6A-modified circRNAs.High glucose (HG)-treated JEG3 cells were used to establish the GDM cell model. Differentially expressed circRNAs levels in GDM and NC groups was measured by qRT-PCR. We knocked down METTL3 to study its function. Additionally, we conducted functional recovery experiments. Dot blot assay was utilized to assess changes in m6A levels. MeRIP-qPCR was performed to evaluate the effect of knocking down METTL3 on m6A modification of hsa_circ_0072380 in JEG3 cells. RESULTS: Compared with NC group, GDM group exhibited increased levels of m6A modification and METTL3 expression. Differences in m6A modification of circRNAs exist between the GDM and NC groups. Hsa_circ_0000994, hsa_circ_0058733, and hsa_circ_0072380 were significantly down-regulated in GDM group while hsa_circ_0036376, hsa_circ_0000471, and hsa_circ_0001173 showed no significant differences between two groups. HG treatment promoted METTL3 expression and m6A level of JEG3 cells, and inhibited cell proliferation, migration, and invasion abilities. Knocking down METTL3 reversed these effects. After HG treatment, hsa_circ_0072380 was significantly down-regulated. Knocking down METTL3 led to up-regulation of hsa_circ_0072380, while knocking down hsa_circ_0072380 restored the function of SiMETTL3. Additionally, knocking down METTL3 significantly reduced m6A modification of hsa_circ_0072380. CONCLUSION: METTL3 mediated m6A modification of hsa_circ_0072380 to regulate GDM progression.

Causal effects of hypertensive disorders of pregnancy on structural changes in specific brain regions: a Mendelian randomization study.

This study utilized Mendelian randomization to explore the impact of hypertensive disorders of pregnancy and their subtypes on brain structures, using genome-wide association study data from the FinnGen consortium for hypertensive disorders of pregnancy exposure and brain structure data from the ENIGMA consortium as outcomes. The inverse-variance weighted method, along with Cochran's Q test, Mendelian randomization-Egger regression, Mendelian randomization-PRESSO global test, and the leave-one-out approach, were applied to infer causality and assess heterogeneity and pleiotropy. Findings indicate hypertensive disorders of pregnancy are associated with structural brain alterations, including reduced cortical thickness in areas like the insula, isthmus cingulate gyrus, superior temporal gyrus, temporal pole, and transverse temporal gyrus, and an increased surface area in the superior frontal gyrus. Specific associations were found for hypertensive disorders of pregnancy subtypes: chronic hypertension with superimposed preeclampsia increased cortical thickness in the supramarginal gyrus; preeclampsia/eclampsia led to thinner cortex in the lingual gyrus and larger hippocampal volume and superior parietal lobule surface area. Chronic hypertension was associated with reduced cortical thickness in the caudal and rostral anterior cingulate and increased surface area of the cuneus and thickness of the pars orbitalis cortex. Gestational hypertension showed no significant brain region changes. These insights clarify hypertensive disorders of pregnancies' neurological and cognitive effects by identifying affected brain regions.

A Qualitative Study on the Experience of Assisted Reproductive Technology in Women with Dyspareunia.

Objective: This study aims to investigate the phenomenon of sexual intercourse-related fear among women utilizing assisted reproductive technology due to dyspareunia. The primary objective is to offer insights that can inform the development of targeted nursing interventions. Methods: Employing a purposive sampling approach, a cohort of 23 female patients experiencing dyspareunia and undergoing treatment at the Reproductive Medicine Center of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2022 and December 2022, were selected as participants for this research. Semi-structured, in-depth interviews were conducted to gather qualitative data. The Colaizzi 7-step analysis method was subsequently applied to scrutinize the interview transcripts and identify emergent themes. Results: The analysis yielded five prominent themes: psychological disturbances, incongruent cognitive perceptions, anticipations regarding conception, insufficient adaptive responses, and sexual expectations. Conclusion: It is imperative for medical practitioners to demonstrate reverence for patients' sexual beliefs and conditions, attune to their apprehensions, and offer efficacious emotional support. Tailored and multifaceted sexual health knowledge should be dispensed based on patients' individual requirements and their envisioned sexual experiences, thereby fostering spousal and familial harmony. By prioritizing patients' sexual well-being, cultivating a compassionate medical milieu, and augmenting the quality of assisted reproductive services, comprehensive improvements can be achieved.

The association between neonatal birthweight discordance and preeclampsia in twin pregnancy.

PURPOSE: To investigate the association between neonatal birthweight (NBW) discordance and preeclampsia (PE) in twin pregnancy. METHODS: This was a single-center retrospective cohort study. Women with two live births in the First Affiliated Hospital of Sun Yat-sen University from January 2011 to June 2020 were eligible. They were classified into four groups based on the quartiles of NBW discordance in monochorionic (MC) and dichorionic (DC) twin pregnancy. The relationship between NBW discordance and the risk of PE was assessed by logistic regression, subgroup analyses was further analyzed. RESULTS: A total of 1566 women were eligible for the final analysis, there were 445 MC cases and 1121 DC cases. No matter in monochorionic or dichorionic pregnancy, higher NBW discordance quartiles were associated with increased risks of PE. Compared with women in the lowest NBW discordance quartile, women in the highest NBW discordance quartile had approximately 3.6 and 6.0 times risk of PE in monochorionic and dichorionic pregnancy respectively. The association between quartiles of NBW discordance and the risk of PE were higher in dichorionic pregnancy than in monochorionic pregnancy. No matter in MC or DC pregnancy, no significant interaction effects were identified for maternal age, pregnancy body mass index, mode of conception and whether complicated with gestational diabetes mellitus. CONCLUSIONS: The increased NBW discordance quartile was related to an increased risk of PE. Assessing estimated fetal weight discordance by using ultrasound in clinical practice to predict PE remained to be further researched.

Decreased FGF23 inhibits placental angiogenesis via the ERK1/2-EGR-1 signaling pathway in preeclampsia.

PURPOSE: This study aimed to investigate the expression of fibroblast growth factor 23 (FGF23) in pregnant women with preeclampsia and elucidate its role in promoting placental angiogenesis through the ERK1/2-EGR-1 signaling pathway. METHODS: Serum FGF23 levels were measured by ELISA in healthy pregnant women and patients with preeclampsia during the first, second, and third trimesters of pregnancy. Wound healing, Transwell, and tube formation assays were performed to investigate the effects of FGF23 on cell migration, invasion and tube formation. The expression of vascular endothelial growth factor A (VEGF-A) and its upstream signaling molecules, p-ERK, and EGR-1, in placental tissues was detected by RT-qPCR and western blotting. Additionally, the effect of FGF23 on VEGF-A, p-ERK, and EGR-1 expression was further explored in vitro. RESULTS: Serum FGF23 levels increased with gestational age. During the third trimester, the control group exhibited a more pronounced increase in FGF23 levels than the preeclampsia group. Administering exogenous FGF23 promoted trophoblast cell migration, invasion and enhanced tube formation in vascular endothelial cells. The expression levels of VEGF-A, p-ERK, and EGR-1 in the placental tissues were significantly lower in the preeclampsia group than in the control group. In vitro experiments confirmed that FGF23 up-regulated VEGF-A expression through the p-ERK/EGR-1 signaling pathway. CONCLUSION: The serum level of FGF23 decreased in pregnant women with preeclampsia, inhibiting the ERK1/2-EGR-1 pathway and resulting in decreased expression of VEGF-A, thereby inhibiting placental angiogenesis. This could be a potential mechanism involved in the progression of preeclampsia.

Novel insights into the complex interplay of immune dysregulation and inflammatory biomarkers in preeclampsia and fetal growth restriction: A two-step Mendelian randomization analysis.

Background: The relationship between genetic immune dysregulation and the occurrence of preeclampsia (PE) or PE with fetal growth restriction (PE with FGR) has yielded inconsistent findings, and the underlying mediators of this association remain elusive. We aimed to explore the causal impact of genetic immune dysregulation on the risk of PE or PE with FGR and to elucidate the role of specific transcriptomes in mediating this relationship. Methods: A two-step Mendelian randomization (MR) analysis was performed to explore the link between immune dysregulation and PE or PE with FGR, as well as to identify potential inflammatory biomarkers that act as mediators. GWAS summary data for outcomes were obtained from the FinnGen dataset. The analyses encompassed five systemic immune-associated diseases, four chronic genital inflammatory diseases, and thirty-one inflammatory biomarkers. Summary-data-based MR (SMR) and HEIDI analysis were conducted to test whether the effect size of single nucleotide polymorphisms (SNPs) on outcomes was mediated by the expression of immune-associated genes. Results: The primary univariable analysis revealed a significant positive correlation between systemic lupus erythematosus (SLE), type 1 diabetes (T1D), type 2 diabetes (T2D), and rheumatoid arthritis (RA) with the risk of PE or PE with FGR. Surprisingly, a counterintuitive finding showed a significant negative association between endometriosis of pelvic peritoneum (EMoP) and the risk of PE with FGR. None of the inflammatory factors had a causal relationship with PE or PE with FGR. However, there was a significant association between lymphocyte count and the risk of PE with FGR. Within the lymphocyte subset, both the proportion of Natural Killer (NK) cells and absolute counts of naïve CD4+ T cells demonstrated significant effects on the risk of PE with FGR. Two-step MR analysis underscored the genetically predicted lymphocyte count as a significant mediator between T1D and PE with FGR. Additionally, SMR analysis indicated the potential involvement of SH2B3 in the occurrence of PE with FGR. Conclusions: Our findings provided substantial evidence of the underlying causal relationship between immune dysregulation and PE or PE with FGR and some of these diseases proved to accelerate immune cells disorders and then contribute to the risk of incident PE or PE with FGR.

Changes in the characteristics and outcomes of high-risk pregnant women who delivered prior to and after China's universal two-child policy: a real-world retrospective study, 2010-2021.

BACKGROUND: In 2016, the "universal two-child" policy, allowing each couple to have two children, was introduced in China. The characteristic change of the long-term period after the implementation of the universal two-child policy was unclear. We studied trends in the obstetric characteristics and their potential impact on the rates of cesarean section and preterm birth in the era of China's universal two-child policy. METHODS: A tertiary center-based study (2010-2021) retrospectively focused single high-risk pregnancies who delivered from the one-child policy period (OCP, 2010-2015) to the universal two-child policy period (TCP, 2016-2021). A total of 39, 016 pregnancies were enrolled. Maternal demographics, complications, delivery mode and obstetric outcomes were analyzed. Furthermore, logistic regression analysis was used to explore the association between the cesarean section rate, preterm birth and implementation of the universal two-child policy, adjusting maternal age, parity, and fetal distress. RESULTS: Ultimately a total of 39,016 pregnant women met the criteria and were included in this analysis. The proportion of women with advanced maternal age (AMA) increased from 14.6% in the OCP to 31.6% in the TCP. The number of multiparous women increased 2-fold in the TCP. In addition, the overall rate of cesarean section significantly decreased over the policy change, regardless of maternal age, whereas the risk of preterm birth significantly increased in the TCP. Adjusting for maternal age, parity and fetal distress, the universal two-child policy showed a significantly favorable impact on the cesarean section rate (RR 0.745, 95%CI (0.714-0.777), P < 0.001). Compared to the OCP group, a higher increase in fetal distress and premature rupture of membranes (PROM) were observed in the TCP group. In pregnancies with AMA, there was no increase in the risk of postpartum hemorrhage, whereas more women who younger than 35 years old suffered from postpartum hemorrhage in TCP. The logistic regression model showed that the universal two-child policy was positively associated with the risk of postpartum hemorrhage (RR: 1.135, 95%CI: 1.025-1.257, P = 0.015). CONCLUSIONS: After the implementation of the universal two-child policy in China, the rate of the cesarean section significantly decreased, especially for women under 35 years old. However, the overall risk of postpartum hemorrhage increased in women under 35 years old, while there was no change in women with AMA. Under the new population policy, the prevention of postpartum hemorrhage in the young women should not be neglected.

Mechanism of BLIMP1/TRIM66/COX2 in human decidua participates in parturition†.

The mechanism underlying the initiation of parturition remains unclear. Cyclooxygenase 2 and prostaglandins in decidual membrane tissue play an important role in the "parturition cascade." With the advancement of gestation, the expression of the transcriptional suppressor B lymphocyte-induced maturation protein 1 in the decidual membrane gradually decreases. Through chromatin immunoprecipitation sequencing, we found that B lymphocyte-induced maturation protein 1 has a binding site in the distal intergenic of PTGS2(COX2). Tripartite motif-containing protein 66 is a chromatin-binding protein that usually performs transcriptional regulatory functions by "reading" histone modification sites in chromatin. In this study, tripartite motif-containing protein 66 exhibits the same trend of expression as B lymphocyte-induced maturation protein 1 in the decidua during gestation. Moreover, the co-immunoprecipitation assay revealed that tripartite motif-containing protein 66 combined with B lymphocyte-induced maturation protein 1. This finding indicated that tripartite motif-containing protein 66 formed a transcription complex with B lymphocyte-induced maturation protein 1, which coregulated the expression of COX2. In animal experiments, we injected si-Blimp1 adenoviruses (si-Blimp1), Blimp1 overexpression plasmid (Blimp1-OE), and Trim66 overexpression plasmid (Trim66-OE) through the tail vein of mice. The results showed that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 affected the initiation of parturition in mice. Therefore, the present evidence suggests that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 partially participate in the initiation of labor, which may provide a new perspective for exploring the mechanism of term labor.

Thyroid autoimmunity and adverse pregnancy outcomes: A multiple center retrospective study.

Background: The relationship between thyroid autoimmunity (TAI) and adverse pregnancy outcomes is disputable, and their dose-dependent association have not been fully clarified. Objective: To investigate the association and dose-dependent effect of TAI with multiple maternal and fetal-neonatal complications. Methods: This study is a multi-center retrospective cohort study based on singleton pregnancies of three medical college hospitals from July 2013 to October 2021. The evolution of thyroid function parameters in TAI and not TAI women were described, throughout pregnancy. The prevalences of maternal and fetal-neonatal complications were compared between the TAI and control group. Logistic regression was performed to study the risk effects and dose-dependent effects of thyroid autoantibodies on pregnancy complications, with adjustment of maternal age, BMI, gravidity, TSH concentrations, FT4 concentrations and history of infertility. Results: A total of 27408 participants were included in final analysis, with 5342 (19.49%) in the TAI group and 22066 (80.51%) in control group. TSH concentrations was higher in TAI women in baseline and remain higher before the third trimester. Positive thyroid autoantibodies were independently associated with higher risk of pregnancy-induced hypertension (OR: 1.215, 95%CI: 1.026-1.439), gestational diabetes mellitus (OR: 1.088, 95%CI: 1.001-1.183), and neonatal admission to NICU (OR: 1.084, 95%CI: 1.004-1.171). Quantitative analysis showed that increasing TPOAb concentration was correlated with higher probability of pregnancy-induced hypertension, and increasing TGAb concentration was positively correlated with pregnancy-induced hypertension, small for gestational age and NICU admission. Both TPOAb and TGAb concentration were negatively associated with neonatal birthweight. Conclusion: Thyroid autoimmunity is independently associated with pregnancy-induced hypertension, gestational diabetes mellitus, neonatal lower birthweight and admission to NICU. Dose-dependent association were found between TPOAb and pregnancy-induced hypertension, and between TGAb and pregnancy-induced hypertension, small for gestational age and NICU admission.

[Important Considerations of Low-Dose Aspirin in the Prevention of Preeclampsia].

Low-dose prophylactic aspirin is widely recommended for pregnant women for the prevention of preeclampsia (PE). Although the efficacy of aspirin in preventing PE has been evaluated in many studies, due to the differences in dosage, initiation time, and screening methods for the identification of women at high risk of PE and the lack of a uniform opinion on the medication regimen of aspirin, currently in China there is no consensus on the standardized treatment scheme of aspirin for the prevention of PE in clinical guidelines. Herein, we reviewed the current available evidence and the recommendations of clinical guidelines concerning the controversies about aspirin dosage as well as the timing of starting and stopping aspirin, so as to provide further guidance for clinical practice. Based on the existing research findings on and clinical practice of using aspirin for PE prevention, we suggested that PE risk screening should be conducted at 11-13+6 weeks of gestation. In addition, the recommended dose for prophylactic use of aspirin for pregnant women at high risk of PE is 150 mg/d, and the recommended minimum effective dose is 100 mg/d. Pregnant women at high risk of PE should start taking low-dose aspirin orally before 16 weeks of pregnancy. Week 36 of gestation is considered the window of opportunity for discontinuation of low-dose aspirin.

Hepatitis C viral load and mother-to-child transmission: A systematic review and meta-analysis.

BACKGROUND AND AIM: We aim to assess the association between maternal hepatitis C virus (HCV) viral load and human immunodeficiency virus (HIV) coinfection and the risk for mother-to-child transmission (MTCT) among pregnant women infected with HCV. METHODS: A literature search of the Medline, Embase, Central, Science Citation Index Expanded (SCIE), Conference Proceedings Citation Index-Science (CPCIS), Scopus, Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS), and WHO Global Index Medicus databases, from inception to June 21, 2022, was performed. Studies that reported the incidence HCV-MTCT were included. Pooled effect estimates were calculated using the random-effects model, and Holm-Bonferroni correction was performed for multiple pooled associations. RESULTS: The present meta-analysis included 26 studies involving 4934 newborns with maternal HCV infection. Pregnant women with HCV viremia exhibited increased risk for MTCT (odds ratio [OR] 8.25 [95% confidence interval (CI) 4.65-14.63]) compared with those negative for HCV-RNA. Multiple subgroup analysis revealed that the HCV viremia/HIV-positive group demonstrated the highest risk for HCV MTCT, followed by the HCV viremia mono-infected group, while HCV-RNA-negative women demonstrated the lowest risk for HCV MTCT. Among females with HCV viremia, elevated risk for MTCT was found among subjects with a viral load ≥ 6 log10 copies/mL compared with those with viral load < 6 log10 copies/mL (OR 4.58 [95% CI: 2.52-8.34]). CONCLUSION: The incidence of HCV MTCT was increased among pregnant women with detectable HCV viremia and was even higher in those with a viral load ≥ 6 log10 copies/mL. HIV coinfection further increased the risk for HCV MTCT.

Optical coherence tomography angiography for the characterisation of retinal microvasculature alterations in pregnant patients with anaemia: a nested case‒control study.

AIMS: To characterise retinal microvascular alterations in the eyes of pregnant patients with anaemia (PA) and to compare the alterations with those in healthy controls (HC) using optical coherence tomography angiography (OCTA). METHODS: This nested case‒control study included singleton PA and HC from the Eye Health in Pregnancy Study. Fovea avascular zone (FAZ) metrics, perfusion density (PD) in the superficial capillary plexus, deep capillary plexus and flow deficit (FD) density in the choriocapillaris (CC) were quantified using FIJI software. Linear regressions were conducted to evaluate the differences in OCTA metrics between PA and HC. Subgroup analyses were performed based on comparisons between PA diagnosed in the early or late trimester and HC. RESULTS: In total, 99 eyes of 99 PA and 184 eyes of 184 HC were analysed. PA had a significantly reduced FAZ perimeter (ß coefficient=-0.310, p<0.001), area (ß coefficient=-0.121, p=0.001) and increased circularity (ß coefficient=0.037, p<0.001) compared with HC. Furthermore, higher PD in the central (ß coefficient=0.327, p=0.001) and outer (ß coefficient=0.349, p=0.007) regions were observed in PA. PA diagnosed in the first trimester had more extensive central FD (ß coefficient=4.199, p=0.003) in the CC, indicating impaired perfusion in the CC. CONCLUSION: It was found that anaemia during pregnancy was associated with macular microvascular abnormalities, which differed in PA as pregnancy progressed. The results suggest that quantitative OCTA metrics may be useful for risk evaluation before clinical diagnosis. TRIAL REGISTRATION NUMBERS: 2021KYPJ098 and ChiCTR2100049850.

Plasma Exosomal miRNAs Associated With Metabolism as Early Predictor of Gestational Diabetes Mellitus.

To date, the miRNA expression profile of plasma exosomes in women whose pregnancy is complicated by gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small-RNA sequencing in 12 pregnant women with GDM and 12 with normal glucose tolerance (NGT) and validated in 102 pregnant women with GDM and 101 with NGT. A total of 22 exosomal miRNAs were found, five of which were verified by real-time qPCR. Exosomal miR-423-5p was upregulated, whereas miR-122-5p, miR-148a-3p, miR-192-5p, and miR-99a-5p were downregulated in women whose pregnancy was complicated by GDM. IGF1R and GYS1 as target genes of miR-423-5p, and G6PC3 and FDFT1 as target genes of miR-122-5p were associated with insulin and AMPK signaling pathways and may participate in the regulation of metabolism in GDM. The five exosomal miRNAs had an area under the curve of 0.82 (95%CI, 0.73, ∼0.91) in early prediction of GDM. Our study demonstrates that dysregulated exosomal miRNAs in plasma from pregnant women with GDM might influence the insulin and AMPK signaling pathways and could contribute to the early prediction of GDM.

Association between lipid trajectories during pregnancy and risk of postpartum glucose intolerance after gestational diabetes mellitus: a cohort study.

AIMS: To assess lipid trajectories throughout pregnancy in relation to early postpartum glucose intolerance in women with gestational diabetes mellitus (GDM). METHODS: This prospective cohort study included 221 Chinese women with GDM who completed plasma lipid test in each trimester of pregnancy and oral glucose tolerance test at 6-9 weeks postdelivery between January 1, 2018 and January 8, 2020. Using the group-based trajectory modeling, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol(HDL-c) were identified separately as three trajectories: low, moderate, and high trajectory. The associations between lipid trajectories and early postpartum glucose intolerance were all evaluated. RESULTS: Seventy-three participants developed postpartum glucose intolerance. For patients in low, moderate and high trajectory, the incidence of postpartum glucose intolerance was 38.4%, 34.9%, and 17.9%, respectively. GDM women with lower LDL-c trajectories presented a higher risk of postpartum glucose intolerance. The adjusted odds ratio (95% CI) for glucose intolerance was 3.14 (1.17-8.39) in low LDL-c trajectory and 2.68 (1.05-6.85) in moderate trajectory when compared with the high one. However, TC trajectory was not associated with the risk of postpartum glucose intolerance, nor were TG trajectory and HDL-c trajectory. Moreover, a significant difference of insulin sensitivity was observed in participants with different LDL-c trajectories; participants in high LDL-c trajectory had the highest insulin sensitivity, whereas the women in low LDL-c trajectory had the lowest insulin sensitivity (P = 0.02). CONCLUSIONS: The high trajectory of LDL-c during pregnancy may play a protective role on postpartum glucose intolerance in women with GDM. Further studies are warranted to explore the underlying mechanism. Trial registration The study was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (reference number: [2014]No. 93). All participants provided written informed consent forms, and the ethics committee approved this consent procedure.

Physical Activity during Pregnancy: Comparisons between Objective Measures and Self-Reports in Relation to Blood Glucose Levels.

OBJECTIVE: to quantify pregnant women's physical activity during pregnancy using wearable accelerometers and a self-reported scale and to examine the variation in these two physical activity measures in relation to fasting plasma glucose (FPG) levels and presence of gestational diabetes mellitus (GDM). METHODS: this prospective observational study included 197 pregnant women from one of the largest regional hospitals in South China. Women with singleton pregnancy, absence of pre-existing comorbidities and pre-specified contraindications, wore an accelerometer on their waist for 7 consecutive days to objectively record their physical activity, followed by completing a past-7-day physical activity questionnaire, three times, respectively, in three trimesters. GDM was determined by 2-h 75 g oral glucose tolerance test (OGTT) in 24-28th week's gestation and FPG was obtained in both 1st and 2nd trimesters following standard practice. RESULTS: pregnant women engaged highest levels of various physical activity types in 2nd trimester, except accelerometer-based moderate-to-vigorous physical activity which gradually decreased in pregnancy. Pregnant women were more likely to walk in 3rd trimester. The relationship between objective total physical activity and self-reported total physical activity was non-linear. Increased trend of FPG from 1st trimester to 2nd trimester disappeared when adjusting for accelerometer-based light physical activity and attenuated when including walking. Self-reported moderate physical activity was surprisingly positively associated with GDM. CONCLUSIONS: different patterns in physical activity between objective measure and self-report in relation to gestational glucose levels were observed. Short-term increase in moderate physical activity prior to OGTT may not be necessary for reducing presence of GDM. Future glucose management for pregnant women may be targeted at lower intensity physical activity.

Food Intake and Diet Quality of Pregnant Women in China During the COVID-19 Pandemic: A National Cross-Sectional Study.

Background: Between January and April 2020, China implemented differentiated prevention and control strategies across the country, based on the severity of the COVID-19 epidemic/pandemic in different regions. These strategies included lockdowns, social distancing, and the closure of public places. These measures may have affected dietary intake to varying degrees. This study aimed to assess variations in food intake and diet quality among pregnant women according to regional severity and related control measures during the most severe period of COVID-19 restrictions in 2020. Methods: A total of 3,678 pregnant women from 19 provinces/municipalities in mainland China were analyzed in this nationwide, multi-center study. Food intake data were obtained and assessed using a validated food frequency questionnaire (FFQ). Diet quality was quantified using the Diet Balance Index for Pregnancy (DBI-P), which included high bound score (HBS, excessive dietary intake), low bound score (LBS, insufficient dietary intake), and diet quality distance (DQD, dietary imbalance). Linear trend tests and multivariable regression analyses were performed to examine the association between food intake, DBI-P and the severity of pandemic. Results: The median daily intake of vegetables, fruit, livestock/poultry meat, dairy, and nuts decreased (p < 0.05) according to low, moderate, and high severity of the pandemic, while no significant differences in cereals/potatoes, eggs, and fish/shrimp intake. The median daily intake of cereals/potatoes exceeded the recommended ranges, and the daily intake of eggs and fish/shrimp was below recommended ranges regardless of the pandemic severity (p < 0.05). Regarding diet quality, HBS decreased (lower excessive consumption) (p = 0.047) and LBS increased (greater insufficient consumption) (p = 0.046) with increased severity of the pandemic. On multivariable analyses, moderate and high pandemic severity were related to lower HBS risk (OR = 0.687, OR = 0.537) and higher LBS risk (ß = 1.517, ß = 3.020) when compared to low pandemic severity. Conclusions: Under more severe COVID-19 pandemic conditions, pregnant women consumed less quality food, characterized by reduced consumption of vegetables, fruit, livestock/poultry meat, dairy and nuts, while the quality of the foods that pregnant women consumed in excess tended to improve, but the overconsumption of cereals/potatoes was a problem.

Clinical outcomes after elective double-embryo transfer in frozen cycles for women of advanced maternal age: A retrospective cohort study.

ABSTRACT: We aimed to determine the clinical outcome of double cleavage-stage embryo transfers in frozen-thawed embryo transfer cycles for older women.This study analyzed a total of 8189 cleavage-stage frozen-thawed embryo transfer cycles between January 2013 and December 2017 at Sir Run Run Shaw Hospital. All cycles were sorted into 3 groups based on patient age: ≤35 years (Group A), 36 to 37 years (Group B), and ≥38 years (Group C). The clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), miscarriage rate, multiple pregnancy rate (MPR), preterm birth rate, and low-birth-weight rate were compared between the 3 groups.Significant differences in CPR, IR, LBR, MPR, and premature birth rate were found among the 3 groups. The CPR, IR, LBR, and MPR in Group A were higher than those in Group C. Transfers of 2 high-quality embryos resulted in significant differences in CPR, IR, LBR, MPR, and neonatal weight among the 3 groups, but no differences in premature birth and abortion rates were observed. Transfers with 1 high-quality and 1 fair-quality embryo resulted in significant differences in CPR, IR, and LBR among the 3 groups. Comparison of transfers of 2 high-quality embryos with 1 high-quality and 1 fair-quality embryo showed that the CPR and LBR were significantly lower for the latter in Groups A and C, but Group B had no salient changes.Higher IR and LBR and lower MPR may be achieved by selection of optimal embryo types for patients of different ages. Two high-quality embryos need to be transferred in women older than 38 years. For women aged 36 to 37 years, 1 high-quality embryo or 1 high-quality plus 1 fair-quality embryo should be singled out for transfer. For women younger than 35 years, a single high-quality embryo should be selected for transfer.

Intrauterine administration of G-CSF for promoting endometrial growth after hysteroscopic adhesiolysis: a randomized controlled trial.

STUDY QUESTION: Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis? SUMMARY ANSWER: Intrauterine perfusion of G-CSF can increase endometrial thickness but does not prevent the recurrence of intrauterine adhesions (IUAs) in patients with Asherman syndrome (AS) after surgery. WHAT IS KNOWN ALREADY: Intrauterine infusion of G-CSF has been used in attempts to treat patients with recurrent miscarriage and an idiopathic thin endometrium for either fresh or frozen-thawed embryo transfer cycles but without uniform efficacy. There have been no reports on the effect of G-CSF on the recurrence of IUAs, endometrial regrowth or pregnancy results in specific populations with AS. STUDY DESIGN, SIZE, DURATION: This two-center prospective double-blind randomized controlled trial ran between April 2016 and August 2021. In it, 245 patients with moderate to severe AS were randomized to G-CSF and control groups at a 1:1 ratio; 229 women were included in the adhesion recurrence analysis; and 164 patients were analyzed for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: All eligible patients received the first hysteroscopic adhesion separation and balloon placement procedure. Patients who met our inclusion and exclusion criteria were randomized after surgery. These patients returned for balloon removal and underwent intrauterine perfusion with 300 µg (1.8 ml) G-CSF or 1.8 ml normal saline according to randomization at 7 days after surgery. A second-look hysteroscopy was carried out 1-2 months later. The primary outcome was the rate of formation of new adhesions at the second hysteroscopy. The secondary outcomes included endometrial thickness in the periovulatory period after surgery, as well as the clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Age, menstrual cycle characteristics, pregnancy history and IUA score before surgery were similar between groups. There were no statistically significant differences in the adhesion reformation rate or median adhesion score reduction. However, G-CSF perfusion significantly improved endometrial thickness (7.91 ± 2.12 mm vs 7.22 ± 2.04 mm; P = 0.019, 95% CI for difference: -1.26 to -0.12), as well as cumulative pregnancy and live birth rate over time (P = 0.017 and P = 0.042). Furthermore, multivariate logistic regression analysis showed that postoperative endometrial thickness was an independent prognostic factor for pregnancy and live birth rates. LIMITATIONS, REASONS FOR CAUTION: These results cannot be extended to older patients or those without AS, as our subjects had moderate or severe AS and were aged <40 years. The low number of patients included in the fertility analysis could lead to biased results. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine perfusion of G-CSF could be an effective adjuvant therapy for patients with AS to increase endometrial thickness. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development Program of China (2018YFC1004800), the National Natural Science Foundation of China (82001624 and 81871209), the Natural Science Foundation of Zhejiang Province (LQ20H040004) and the provincial and ministerial construction project of Zhejiang Province (2017 WKJ-ZJ-1721). The authors declare that they have no conflicts of interest regarding this work. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02855632). TRIAL REGISTRATION DATE: 4 March 2016. DATE OF FIRST PATIENT'S ENROLMENT: 13 April 2016.

Health-Related Quality of Life Among Pregnant Women With Pre-pregnancy Smoking and Smoking Cessation During Pregnancy in China: National Cross-sectional Study.

BACKGROUND: Previous studies have hardly explored the influence of pre-pregnancy smoking and smoking cessation during pregnancy on the health-related quality of life (HRQoL) of pregnant women, which is a topic that need to be addressed. In addition, pregnant women in China constitute a big population in the largest developing country of the world and cannot be neglected. OBJECTIVE: This study aims to evaluate the HRQoL of pregnant women in China with different smoking statuses and further estimate the association between pre-pregnancy smoking, smoking cessation, and the HRQoL. METHODS: A nationwide cross-sectional study was conducted to determine the association between different smoking statuses (smoking currently, quit smoking, never smoking) and the HRQoL in pregnant women across mainland China. A web-based questionnaire was delivered through the Banmi Online Maternity School platform, including questions about demographics, smoking status, and the HRQoL. EuroQoL Group's 5-dimension 5-level (EQ-5D-5L) scale with EuroQoL Group's visual analog scale (EQ-VAS) was used for measuring the HRQoL. Ethical approval was granted by the institutional review board of the First Affiliated Hospital of Sun Yat-sen University (ICE-2017-296). RESULTS: From August to September 2019, a total of 16,483 participants from 31 provinces were included, of which 93 (0.56%) were smokers, 731 (4.43%) were ex-smokers, and 15,659 (95%) were nonsmokers. Nonsmokers had the highest EQ-VAS score (mean 84.49, SD 14.84), smokers had the lowest EQ-VAS score (mean 77.38, SD 21.99), and the EQ-VAS score for ex-smokers was in between (mean 81.04, SD 17.68). A significant difference in EQ-VAS scores was detected between nonsmokers and ex-smokers (P<.001), which indicated that pre-pregnancy smoking does have a negative impact on the HRQoL (EQ-VAS) of pregnant women. Compared with nonsmokers, ex-smokers suffered from more anxiety/depression problems (P=.001, odds ratio [OR] 1.29, 95% CI 1.12-1.50). Among ex-smokers, the increased cigarette consumption was associated with a lower EQ-5D index (P=.007) and EQ-VAS score (P=.01) of pregnant women. Compared to smokers, no significant difference was found in the ex-smokers' EQ-5D index and EQ-VAS score (P=.33). CONCLUSIONS: Smoking history is associated with a lower HRQoL in pregnant Chinese women. Pre-pregnancy smoking is related to a lower HRQoL (EQ-VAS) and a higher incidence of depression/anxiety problems. Smoking cessation during pregnancy does not significantly improve the HRQoL of pregnant Chinese women. Among ex-smokers, the more cigarettes they smoke, the lower HRQoL they have during pregnancy. We suggest that the Chinese government should strengthen the education on quitting smoking and avoiding second-hand smoke for women who have pregnancy plans and their family members.

Longitudinal trends in lipid profiles during pregnancy: Association with gestational diabetes mellitus and longitudinal trends in insulin indices.

Objective: To investigate the correlation of trends in lipid profiles from first to second trimester with trends in insulin indices and gestational diabetes mellitus (GDM). Methods: Secondary analysis of an ongoing prospective cohort study was conducted on 1234 pregnant women in a single center. Lipid profiles, glucose metabolism and insulin indices were collected in the first and second trimesters. Trends in lipid profiles were divided into four subgroups: low-to-low, high-to-high, high-to-low and low-to-high group. Insulin indices including homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were calculated to evaluate insulin resistance (IR). Trends in insulin indices were described as: no IR, persistent IR, first-trimester IR alone and second-trimester IR alone. Pearson correlation analysis and multivariate logistic regression were performed to assess the associations of lipid profiles subgroups with insulin indices and GDM. Results: First- and second-trimester total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol were strongly correlated to first- and second-trimester insulin indices. Only TG had a sustained correlation with glucose metabolism indices. High-to-high low-density lipoprotein cholesterol (LDL-c) was an independent risk factor for GDM. High-to-high TG and high-to-low TG groups were independent risk factors for persistent IR. High-to-high TG and low-to-high TG groups were independent risk factors for second-trimester IR alone. Conclusion: TG has a sustained correlation with insulin indices and glucose metabolism indices. Persistently high TG is an independent risk factor for persistent IR and second-trimester IR alone. Regardless of whether pregnant women have first-trimester IR, lower TG levels help reduce the risk for persistent IR or subsequent development of IR. These results highlight the benefit of lowering TG levels in early and middle pregnancy to prevent the development of IR.