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Risk factors analysis and prediction model construction of major adverse cardiovascular events in pregnant women with valvular heart disease

Objective: To analysis the risk factors for major adverse cardiovascular event (MACE) in pregnant women with valvular heart disease (VHD) and to construct a risk prediction model. Methods: The clinical data of 245 pregnant women with VHD who were hospitalized in Beijing Anzhen Hospital from January 1, 2012, to June 1, 2023 were retrospectively analyzed, including general information, pre-pregnancy and pregnancy-associated cardiac conditions, and MACE. Univariate analysis and logistic regression models were employed to identify risk factors for MACE during pregnancy among pregnant women with VHD. Furthermore, a predictive model was constructed and internal validation was conducted using bootstrap techniques. Results: (1) Among 245 pregnant women with VHD, the incidence of MACE was 18.0% (44/245), and the most common MACE was heart failure (61.4%, 27/44). The mitral valve was the most frequently affected valve (64.9%, 159/245). Prior to pregnancy, the most common type of valve surgery undertaken was mechanical valve replacement, representing 31.4% (77/245) of surgeries. In contrast, among those pregnant women who did not undergo valve surgery before pregnancy, the most common lesion type was mitral regurgitation (17.6%, 43/245). (2) Comparing the maternal and infant outcomes of warfarin, low molecular weight heparin (LMWH) and LMWH sequential with warfarin, the fetal loss rate (36%, 15/42) and malformation rate (7%, 3/42) were the highest, but the MACE rate (12%, 5/42) was the lowest in warfarin group. The fetal loss rate (1/19), malformation rate (1/19) and artificial valve thrombosis rate (0) of LMWH sequential with warfarin were the lowest, and the fetal loss rate and artificial valve thrombosis rate of the three anticoagulation methods were statistically significant (all P<0.05). (3) There were no significant differences in gestational age, age of diagnosis of heart disease, weight at delivery, pre-pregnancy body mass index, proportion of multiparous women and chronic medical history between women with MACE and those without MACE (all P>0.05). (4) Binary logistic regression analysis identified the following as risk factors for MACE during the second trimester of pregnancy among pregnant women with VHD: pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH during pregnancy, and arrhythmia (all P<0.05). Based on the results of multivariate analysis, a receiver operating characteristic curve was constructed, with an area under the curve of 0.837, indicating good discriminative ability. The calibration plot demonstrated a close alignment between the standard curve and the calibration prediction curve, suggesting excellent calibration of the model. Conclusions: Pregnant women with VHD are at a high risk of experiencing MACE during gestation. Five risk factors, including pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH, and arrhythmia, could aid in identifying high-risk pregnant women.

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Characteristics and maternal-fetal outcomes of pregnant women with critical congenital heart disease from a single center in China

Objective: To summarize the characteristics of pregnant women with critical congenital heart disease, and to explore continuous, integrated, multidisciplinary management for this segment of population. Methods: The clinical records of pregnant women with severe congenital heart disease with a history of intensive care who were treated in Guangdong Provincial People's Hospital from January 1, 2008 to December 31, 2020 were retrospectively analyzed. Results: (1) A total of 132 cases were included, including 128 pregnant women [gestational age (28.0±8.8) weeks] and 4 puerpera cases (6-32 days postpartum), 63.6% (84/132) from economic underdeveloped rural areas, and 78.0% (103/132) by the municipal hospital, irregular prenatal examination accounted for 59.1% (78/132). The main type of congenital heart disease was shunt lesion (55.3%, 73/132). 90.9% (120/132) with mWHO risk classification stage Ⅳ were assigned to it. The main cardiovascular complication was pulmonary hypertension (64.4%, 85/132). 46.2% (61/132) of the patients had been diagnosed with congenital heart disease before pregnancy, and 70.5% (93/132) of the patients had not received any treatment before pregnancy. (2) All patients received obstetric-led, multidisciplinary care. The rescue success rate was 96.2% (127/132), and no serious obstetric complications occurred. The mortality within 24 hours after discharge was 3.8% (5/132). 16.7% (22/132) underwent cardiac surgery during pregnancy, of which 77.3% (17/22) continued their pregnancy beyond 34 weeks. Totally, the delivery week was (30.5±8.6) weeks, and the main mode was cesarean section (71.2%, 94/132). The average weight of 99 live births (including 1 twin pregnancy) was (2 167±698) g. Preterm birth, fetal growth restriction, and congenital malformations were the main fetal comorbidities. Conclusions: Pregnant women with severe congenital heart disease mainly come from areas with underdeveloped economic and medical levels. Later disease intervention, pregnancy retention despite of clear pregnancy contraindications are the distinctive features, which leaded to a significant increase of incidence of maternal and fetal complications, and an increase of the consumption of medical resources. Multidisciplinary active treatment and cardiac surgery during pregnancy could relatively improve maternal and fetal pregnancy outcomes.

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Application of the blastomere count variations "skip value" in the embryo AI assessment

Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the β values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number (β=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate (OR=0.97, 95%CI: 0.93-0.99, P=0.034; OR=0.96, 95%CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age (OR=0.91, 95%CI: 0.88-0.93; P<0.001), D3 general score (OR=0.77, 95%CI: 0.59-0.99; P=0.045) and order selection of skip values (OR=0.98, 95%CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred (OR=1.08, 95%CI:1.05-1.11, P<0.001; OR=1.09, 95%CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.

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Sexual functional outcomes of vaginal dilation therapy for MRKH syndrome: a prospective study

Objectives: To report the sexual functional outcomes of vaginal dilation therapy in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients. Methods: From March 2020 to February 2023, 97 MRKH syndrome patients performed vaginal dilation therapy with guidance from Peking Union Medical College Hospital, and 45 of them engaged in penetrative intercourse and were included in this prospective cohort study. The Chinese version of female sexual function index (FSFI) was used to assess sexual function. Functional success was defined as FSFI>23.45. Forty age-matched healthy women were selected as controls. Kaplan-Meier survival analysis was used to calculate the median time to success. Pearson correlation analysis was used to explore the relationship between neovagina length and sexual function. Complications were collected using follow-up questionnaires. Results: The functional success rate of vaginal dilation therapy was 89% (40/45) with a median time to success of 4.3 months (95%CI: 3.0-6.1 months). Compared to controls, MRKH syndrome patients had significantly lower scores in the orgasm domain (4.72±1.01 vs 4.09±1.20; P=0.013) and pain domain (5.03±0.96 vs 4.26±0.83; P<0.001). However, there were no significant differences in the FSFI total score (26.77±2.70 vs 26.70±2.33; P=0.912), arousal domain (4.43±0.77 vs 4.56±0.63; P=0.422) and satisfaction domain (4.88±0.98 vs 4.65±0.86; P=0.269) between MRKH syndrome patients and controls. MRKH syndrome patients had significantly higher scores in the desire domain (3.33±0.85 vs 3.95±0.73; P<0.001) and lubrication domain (4.37±0.56 vs 5.20±0.67; P<0.001). The prevalence of sexual dysfunction in MRKH patients was non-inferior to controls: low desire [3% (1/40) vs 23% (9/40); P=0.007], arousal disorder [3% (1/40) vs 3% (1/40); P>0.999], lubrication disorder [5% (2/40) vs 25% (10/40); P=0.012], orgasm disorder [40% (16/40) vs 20% (8/40); P=0.051], sexual pain [30% (12/40) vs 15% (6/40); P=0.108]. Conclusions: MRKH syndrome patients undergoing non-invasive vaginal dilation therapy could achieve satisfactory sexual life. Given its high functional success rate and slight complication, vaginal dilation therapy should be recommended as the first-line option, reducing the need for unnecessary surgeries.

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Fetoscopy for intrauterine diagnosis and treatment of amniotic band syndrome: a clinical analysis of 7 cases and literature review

Objective: To summarize the clinical value of fetoscopy in the prenatal diagnosis and treatment of amniotic band syndrome (ABS). Methods: A retrospective analysis was conducted on the clinical data of seven ABS fetuses who underwent prenatal fetoscopic intervention at the Third Affiliated Hospital of Zhengzhou University from December 2020 to August 2023. Literatures related to fetoscopic treatment of ABS were searched in databases including China National Knowledge Infrastructure, Wanfang Data, and PubMed. Clinical data were extracted and the characteristics and intervention effects of fetoscopic surgery in the treatment of ABS were summarized. Results: (1) Preoperative evaluation: the gestational age at diagnosis for the seven ABS fetuses was (19.8±4.4) weeks, and the gestational age at fetoscopic intervention was (22.2±2.8) weeks. The indications for fetoscopic intervention included umbilical cord involvement (3 cases), limb amniotic band with circular constriction (2 cases), and unclear visualization of digits (3 cases). (2) Pregnancy outcomes: among the seven ABS fetuses, four cases underwent selective termination of pregnancy due to severe intrauterine limb amputation, and three cases underwent fetoscopic lysis of amniotic bands. Among the latter three cases, one case experienced intrauterine fetal death (IUFD) two weeks after the procedure, and two cases had good postoperative outcomes. (3) Literature review: a total of 40 cases, including 37 cases from 17 articles and three cases from our institution, were included in the analysis. The indications for fetoscopic surgery included limb amniotic band with circular constriction and involvement of the umbilical cord. The success rate of the surgery was 82% (33/40), and 78% (29/37) of the affected limbs retained good functionality. Premature rupture of membranes was the most common complication, with an incidence rate of 48% (16/33). The average interval from the surgery to membrane rupture was (6.1±5.1) weeks, and the average interval from the surgery to delivery was (10.5±4.1) weeks, with an average gestational age at delivery of (33.7±3.6) weeks. The pregnant women were divided into single Trocar group (27 cases) and double Trocar group (13 cases) based on the surgical approach. The success rates in single Trocar group and double Trocar group were 78% (21/27) and 12/13, respectively, and the difference was not statistically significant (χ2=0.474, P=0.491). The gestational age of delivery in the single Trocar group and double Trocar group was (32.7±3.4) and (35.4±3.2) weeks, respectively, and the difference was statistically significant (t=-2.185, P<0.05). There were no statistically significant differences in the success rate of the surgery, incidence of premature rupture of membranes, interval between surgery and membrane rupture, interval between surgery and delivery, and preterm delivery rate between the two groups (all P>0.05). Conclusions: Fetoscopy could be used for prenatal assessment and intrauterine treatment of ABS. Fetoscopic lysis of amniotic bands may be an effective method for treating ABS, which helps preserve limb function and prevent intrauterine limb amputation and IUFD.

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Relationship between amniotic fluid inflammatory factors and pregnancy outcomes after emergency cervical cerclage

Objective: To explore the relationship between amniotic fluid and peripheral blood inflammatory factors and the pregnancy outcomes after emergency cervical cerclage, and to identify effective indicators for predicting adverse pregnancy outcomes after the procedure. Methods: A case-control study was conducted, including pregnant women who were hospitalized at Sun Yat-sen Memorial Hospital, from January 1, 2013, to July 31, 2019, and underwent emergency cervical cerclage due to cervical dilatation at gestational age between 16 and 28 weeks. A total of 85 pregnant women who underwent amniocentesis for the detection of amniotic fluid inflammatory factors during the perioperative period were included. Based on whether their baby was perinatal death, the participants were divided into the case group (28 cases with perinatal death) and the control group (57 cases with live births). Univariate logistic regression analysis was performed to identify risk factors associated with adverse pregnancy outcomes, followed by multivariate logistic regression analysis to establish a regression model and nomogram. Results: (1) The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10 in the amniotic fluid during the perioperative period and postoperative serum C-reactive protein (CRP) were significantly higher in the case group compared to the control group (all P<0.05). The case group underwent emergency cervical cerclage at an earlier gestational age compared to the control group, and their cervical dilation was greater than that of the control group (all P<0.05). However, there were no significant differences in the white blood cell counts, neutrophil percentage, and the level of preoperative CRP in the peripheral blood of pregnant women during the perioperative period (all P>0.05). (2) Univariate logistic regression analysis showed that the levels of amniotic fluid WBC, TNF-α, IL-1β, IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, postoperative CRP in the peripheral blood, gestational age at cerclage and cervical dilation were associated with adverse pregnancy outcomes (all P<0.05). Multivariate regression analysis indicated that only the levels of amniotic fluid WBC and TNF-α were independent risk factors for perinatal death. (3) Based on clinical practice, a multivariate logistic regression model was constructed including the levels of amniotic fluid TNF-α, WBC, gestational age at cervical cerclage, and cervical dilation. A nomogram and calibration curve were plotted, which suggested its good predictive value for adverse pregnancy outcomes. Conclusions: During the perioperative period of emergency cervical cerclage, the levels of amniotic fluid WBC, TNF-α, IL-1β, IL-2R, IL-6, IL-8, IL-10 are associated with adverse pregnancy outcomes, with amniotic fluid WBC and TNF-α showing the closest relationship. However, there is no significant correlation between maternal peripheral hemogram during the perioperative period and adverse pregnancy outcomes. A model constructed by amniotic fluid TNF-α, WBC, cervical cerclage gestational age, and cervical dilation has a good predictive effect on adverse pregnancy outcomes.

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