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Antibiotic resistome has emerged as a global threat to public health. However, gestational antibiotic resistome and potential link with adverse pregnancy outcomes remains poorly understood. Our study reports for the first time an association between gut antibiotic resistome during early pregnancy and the risk of gestational diabetes mellitus (GDM) based on a prospective nested case-control cohort including 120 cases and 120 matched controls. A total of 214 antibiotic resistance gene (ARG) subtypes belonging to 17 ARG types were identified in > 10 % fecal samples collected during each trimester. The data revealed dynamic profiles of gut antibiotic resistome through pregnancy, and significant positive associations between selected features (i.e., ARG abundances and a GDM-ARG score which is a new feature characterizing the association between ARGs and GDM) of gut antibiotic resistome during early pregnancy and GDM risk as well as selected endogenous metabolites. The findings demonstrate ubiquitous presence of ARGs in pregnant women and suggest it could constitute an important risk factor for the development of GDM.
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BACKGROUND: Inconsistent associations between antenatal depression and fetal birth weight were reported previously, and little is known about the dynamic changes and long-term cumulative effect of antenatal depression during pregnancy. METHODS: Participants were from the Tongji-Huaxi-Shuangliu Birth Cohort. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale in early, middle, and late pregnancy respectively. Trajectories of antenatal depression were assessed using the latent class mixed model. The percentage of days with depression (PDD) and frequency of antenatal depression were measured to assess the cumulative exposure. Multivariable logistic regression models were used to evaluate the associations of antenatal depression with macrosomia and large for gestational age (LGA). RESULTS: We identified four distinct trajectories, including the low stable group (n = 1,327, 27.99 %), the moderate stable group (n = 2,610, 55.05 %), the peak group (n = 407, 8.58 %), and the valley group (n = 397, 8.37 %). Compared with the low stable group, the valley group showed a higher risk of macrosomia (OR, 1.98; 95 % CI, 1.17, 3.38) and LGA (OR, 1.44; 95 % CI, 1.002, 2.09); the peak group showed a higher risk of LGA (OR, 1.52; 95 % CI, 1.07, 2.16), but the association was not significant for macrosomia (OR, 1.47; 95 % CI, 0.85, 2.55). Consistently, cumulative antenatal depression was also positively associated with the risks of macrosomia and LGA. LIMITATION: The antenatal depression was self-reported using a screening scale and information bias could not be ruled out. CONCLUSION: Certain trajectories and cumulative exposure of antenatal depression were associated with higher risks of high birth weight.
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Peso al Nacer , Depresión , Macrosomía Fetal , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Macrosomía Fetal/epidemiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Depresión/epidemiología , Depresión/psicología , China/epidemiología , Recién Nacido , Factores de Riesgo , Estudios de Cohortes , Modelos Logísticos , Escalas de Valoración Psiquiátrica , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicologíaRESUMEN
OBJECTIVE: To evaluate the effectiveness of the YEARS algorithm for excluding pulmonary embolism (PE) in hospitalized women after cesarean section. METHODS: This retrospective study included postpartum women who gave birth by cesarean section and received computed tomography pulmonary angiography (CTPA) because of suspected PE in the obstetric department between 2015 and 2021. We used the YEARS algorithm in these women retrospectively and assessed its performance to evaluate whether the algorithm could be reliably applied in such cases. RESULTS: In all, 225 women were included in the study, of whom 29 (12.9%) women were positive for PE according to the results of CTPA. Upon retrospective application of the YEARS algorithm, 188 (83.6%) women had no YEARS items, while 37 (16.4%) women had YEARS items. Combining the results with D-dimer levels revealed that only 12 (5.3%) women did not need to undergo CTPA, and none showed PE. CONCLUSION: The YEARS algorithm could be applied to exclude PE in hospitalized women in the early post-cesarean period. However, the specificity of the YEARS algorithm was very low, and the D-dimer cut-off for ruling out PE in women after early cesarean section should be further studied and optimized.
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OBJECTIVE: The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. DESIGN: Based on a prospective birth cohort in central China (2017 to 2020): Tongji-Huaxi-Shuangliu Birth Cohort, we included 4800 participants who had available ITS2 sequencing data, dietary information and clinical records during their pregnancy. Additionally, we established a subcohort of 1059 participants, which included 514 women who gave birth to preterm, low birthweight or macrosomia infants, as well as 545 randomly selected controls. In this subcohort, a total of 750, 748 and 709 participants had ITS2 sequencing data, 16S sequencing data and serum metabolome data available, respectively, across all trimesters. RESULTS: The composition of gut fungi changes dramatically from early to late pregnancy, exhibiting a greater degree of variability and individuality compared with changes observed in gut bacteria. The multiomics data provide a landscape of the networks among gut mycobiome, biological functionality, serum metabolites and pregnancy health, pinpointing the link between Mucor and adverse pregnancy outcomes. The prepregnancy overweight status is a key factor influencing both gut mycobiome compositional alteration and the pattern of metabolic remodelling during pregnancy. CONCLUSION: This study provides a landscape of gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health, which lays the foundation of the future gut mycobiome investigation for healthy pregnancy.
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Microbioma Gastrointestinal , Micobioma , Humanos , Femenino , Embarazo , Microbioma Gastrointestinal/fisiología , Adulto , Estudios Prospectivos , China , Metaboloma , Hongos/aislamiento & purificación , Recién NacidoRESUMEN
BACKGROUND: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants during pregnancy. It is considered to be the drug of choice due to its safety in not crossing placenta. Considering the beneficial effect in the improvement of microcirculation, prophylactic application of LMWH in patients with preeclampsia became a trend. However, the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated. This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia. CASE SUMMARY: Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy. All the cases experienced catastrophic hemorrhagic events. After reviewing the twenty-one meta-analyses, the bleeding risk related with LMWH seems ignorable. Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH. Other studies reported minor bleeding risks, none of these were serious enough to stop LMWH treatment. Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored. Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial. CONCLUSION: Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.
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PURPOSE: The "en caul" cesarean section (CS) is a method to keep the amnion intact during CS. This amnion protection effect may have benefits in preterm twin pregnancy. This study aimed to explore the benefits and risks of this method in preterm twin pregnancy. METHODS: This study is a retrospective analysis of preterm twin pregnancies underwent CS in West China Second University Hospital of Sichuan University from January 2011 to December 2022. Data on maternal and fetal outcomes were collected. Univariable analyses and multivariate logistic regression analyses were applied. The level of significance was set at p < 0.05. RESULTS: A total of 182 patients were included (90 in the "en caul" group, 92 in the conventional group). "en caul" CS was associated with lower incidence for respiratory distress (aOR 0.47, 95% CI 0.25-0.88, for the first fetus; aOR 0.42, 95% CI 0.21-0.82, for the second fetus). This method was proved to have beneficial effects in improving the Apgar scores at 1st minute and reducing the mechanical ventilation rate in the second neonates (aOR 0.41, 95% CI 0.19-0.88). CONCLUSION: "En caul" CS is an easy and safe technique to perform during CS for preterm twin pregnancy. The efficacy and safety of this method could be tested by future studies with larger sample size.
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Cesárea , Embarazo Gemelar , Humanos , Embarazo , Femenino , Cesárea/estadística & datos numéricos , Estudios Retrospectivos , Adulto , Recién Nacido , Puntaje de Apgar , Amnios , China/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & control , Nacimiento Prematuro/prevención & control , Nacimiento Prematuro/epidemiologíaRESUMEN
Trace elements are important components in the body and have fundamental roles in maintaining a healthy and balanced pregnancy process. Either deficiency or excess of trace elements, including selenium, iron, zinc, copper, and magnesium can lead to pregnancy complications. As a rare disorder during pregnancy of unknown aetiology, intrahepatic cholestasis of pregnancy (ICP) poses a significant risk to the fetus of perinatal mortality. ICP is a multifactorial complication of which the pathogenesis is still an enigma. Epidemiological studies have demonstrated the association of ICP with some trace elements. Evidence from retrospective studies in humans further revealed the possible contributing roles of trace elements in the pathogenesis of ICP. The published literature on the association of trace elements with ICP was reviewed. Recent advances in molecular biological techniques from animal studies have helped to elucidate the possible mechanisms by how these trace elements function in regulating oxidative reactions, inflammatory reactions and immune balance in the maternal-fetal interface, as well as the influence on hepato-intestinal circulation of bile acid. The scenario regarding the role of trace elements in the pathogenesis of ICP is still developing. The administration or depletion of these trace elements may have promising effects in alleviating the symptoms and improving the pregnancy outcomes of ICP.
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Colestasis Intrahepática , Complicaciones del Embarazo , Oligoelementos , Colestasis Intrahepática/metabolismo , Humanos , Femenino , Complicaciones del Embarazo/metabolismo , Embarazo , Oligoelementos/metabolismo , Animales , Zinc/metabolismo , Zinc/deficienciaRESUMEN
Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.
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In patients with mechanical heart valve protheses, warfarin is usually recommended because of its exceptional anticoagulation effects. However, warfarin can cross the placenta, leading to teratogenicity and even catastrophic hemorrhage in the fetus. The present article describes a case of warfarin-associated fetal intracranial hemorrhage. The patient was a woman in her early 30s. At the age of 11 years, she had undergone aortic valve replacement (mechanical) for aortic regurgitation. Since then, she had been taking oral warfarin. During her pregnancy, her prothrombin time-international normalized ratio was maintained between 1.5 and 2.5. At 35 weeks of gestation, fetal ultrasonography revealed an intracranial mass in the left hemisphere. An emergency cesarean section was performed because fetal intracranial hemorrhage was suspected. A male infant was delivered with a 1- 5-, and 10-minute Apgar score of 1, 5, and 7, respectively. Cranial computed tomography revealed multiple hemorrhage sites with newly emerged bleeding spots. In patients with mechanical heart valve protheses, obstetricians face the dilemma of individual-patient differences and the difficulty of intensive monitoring of the coagulation parameters in the fetus. Tailor-made anticoagulation therapy and a more intensive ultrasonic monitoring strategy, even that involving regular magnetic resonance imaging, are necessary in these patients.
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Prótesis Valvulares Cardíacas , Warfarina , Humanos , Masculino , Embarazo , Femenino , Niño , Warfarina/efectos adversos , Anticoagulantes/efectos adversos , Madres , Cesárea , Hemorragia , Feto , Prótesis Valvulares Cardíacas/efectos adversos , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/diagnóstico por imagenRESUMEN
CONTEXT: Chronic low-grade inflammation may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, prospective studies on the relations of inflammatory blood cell parameters during pregnancy with GDM are lacking. OBJECTIVE: To prospectively investigate the associations of inflammatory blood cell parameters in both early and middle pregnancy, and their change patterns from early to middle pregnancy, with GDM risk. METHODS: We used data from the Tongji-Shuangliu Birth Cohort. Inflammatory blood cell parameters (white blood cells [WBC], neutrophils, lymphocytes, monocytes, neutrophil to lymphocyte ratio [NLR], and platelets) were assayed before 15 weeks and between 16 and 28 weeks of gestational age. Logistic regression was used to evaluate the associations between inflammatory blood cell parameters and GDM. RESULTS: Of the 6354 pregnant women, 445 were diagnosed with GDM. After adjustment for potential confounders, WBC, neutrophils, lymphocytes, monocytes, and NLR in early pregnancy were positively associated with GDM risk (odds ratios [95% CI] for extreme-quartile comparison were 2.38 [1.76-3.20], 2.47 [1.82-3.36], 1.40 [1.06-1.85], 1.69 [1.27-2.24], and 1.51 [1.12-2.02], respectively, all P for trend ≤ .010). Similarly, higher levels of WBC, neutrophils, monocytes, and NLR in middle pregnancy were associated with increased risk of GDM (all P for trend ≤ .014). Stable high levels (≥ median in both early and middle pregnancy) of WBC, neutrophils, monocytes, and NLR were positively associated with GDM risk (all P ≤ .001). CONCLUSION: Increased WBC, neutrophils, monocytes, and NLR in both early and middle pregnancy and their stable high levels from early to middle pregnancy were associated with higher GDM risk, highlighting that they might be clinically relevant for identifying individuals at high risk for GDM.
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Diabetes Gestacional , Embarazo , Femenino , Humanos , Estudios Prospectivos , Primer Trimestre del Embarazo , Neutrófilos , Glucemia , Inflamación/complicacionesRESUMEN
BACKGROUND: Evidence regarding prepregnancy weight change and gestational diabetes mellitus (GDM) is lacking among East Asian women. OBJECTIVES: Our study aimed to investigate the association between weight change from age 18 y to pregnancy and GDM in Chinese pregnant women. METHODS: Our analyses included 6972 pregnant women from the Tongji-Shuangliu Birth Cohort. Body weights were recalled for age 18 y and the time point immediately before pregnancy, whereas height was measured during early pregnancy. Prepregnancy weight change was calculated as the difference between weight immediately before pregnancy and weight at age 18 y. GDM outcomes were ascertained by 75-g oral-glucose-tolerance test. Multivariable logistic regression models were used to examine the association between prepregnancy weight change and risk of GDM. RESULTS: In total, 501 (7.2%) developed GDM in the cohort. After multivariable adjustments, prepregnancy weight change was linearly associated with a higher risk of GDM (P < 0.001). Compared with participants with stable weight (weight change within 5.0 kg) before pregnancy, multivariable-adjusted odds ratios and 95% confidence intervals were 1.55 (1.22, 1.98) and 2.24 (1.78, 2.83) for participants with moderate (5-9.9 kg) and high (≥10 kg) weight gain, respectively. In addition, overweight/obesity immediately before pregnancy mediated 17.6% and 31.7% of the associations of moderate and high-weight gain with GDM risk, whereas weekly weight gain during pregnancy mediated 21.1% and 22.7% of the associations. CONCLUSIONS: Weight gain from age 18 y to pregnancy was significantly associated with a higher risk of GDM. Maintaining weight stability, especially prevention of excessive weight gain from early adulthood to pregnancy, could be a potential strategy to reduce GDM risk.
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Diabetes Gestacional , Aumento de Peso , Adolescente , Adulto , Femenino , Humanos , Embarazo , Índice de Masa Corporal , Pueblos del Este de Asia , Sobrepeso/complicaciones , Mujeres Embarazadas , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. METHODS: In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. RESULTS: Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. CONCLUSIONS: Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.
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Diabetes Gestacional , Embarazo , Femenino , Humanos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Estudios Prospectivos , Mujeres Embarazadas , Factores de Riesgo , Pueblos del Este de Asia , Hígado , Biomarcadores , LípidosRESUMEN
BACKGROUND: Venous thromboembolism (VTE) is one of the primary causes of maternal death. Although many studies have reported maternal VTE, no study has estimated the incidence of it in China. OBJECTIVES: The aim of this work was to estimate the incidence of maternal VTE in China and to compare the risk factors for it. SEARCH STRATEGY: The authors searched eight platforms and databases including PubMed, Embase, and Cochrane Library from inception to April 2022, with the search terms "venous thromboembolism" AND "puerperium (pregnancy)" AND "incidence" AND "China." SELECTION CRITERIA: Studies provide data to calculate the incidence of maternal VTE among Chinese patients. DATA COLLECTION AND ANALYSIS: The authors made a standardized table to collect data and calculated the incidence and 95% confidence intervals (CIs), founding source of heterogeneity by subgroup analysis and meta-regression and judging publication bias by funnel plot and Egger test. MAIN RESULTS: The included 53 papers with a total sample size of 3 813 871 patients had 2539 cases of VTE, and the incidence of maternal VTE in China was 0.13% (95% CI, 0.11-0.16; P < 0.001). CONCLUSIONS: The trend in the incidence of maternal VTE in China is stable. Cesarean section and advanced age are associated with a higher incidence of VTE.
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Tromboembolia Venosa , Humanos , Embarazo , Femenino , Tromboembolia Venosa/epidemiología , Cesárea/efectos adversos , Factores de Riesgo , Periodo Posparto , Familia , AnticoagulantesRESUMEN
In intrahepatic cholestasis of pregnancy (ICP) patients, high concentrations of bile acids altered the normal maternal-fetal-unit physiological condition and could bring negative influence on placenta functionality. GABRP is the pi subunit of the gamma-aminobutyric acid type A receptor (GABAA) and plays pivotal role in regulating GABAA receptor's physiological function. Here we presented evidence that increased expression of GABRP in parallel with autophagic biomarkers, LC3 and ATG14, in patients with ICP. METHODS: A total of 27 participants, including 18 ICP patients and 9 healthy pregnancies were recruited according to strict inclusion criteria. Placentas of ICP patients and controls were collected immediately after cesarean section before labor onset. GABRP and autophagic markers expression in placenta were investigated by immunohistochemistry (IHC), RT-qPCR, and Western blot. RESULTS: The neonatal birthweight and gestational weeks were significantly lower in severe ICP group, while the hepatic enzymes were elevated in ICP group. Semiquantitative analysis of IHC revealed the AOD of GABRP in severe ICP patients was higher than that in mild ICP patients and control pregnancies. Western blot and RT-qPCR analysis both indicated that the expression of GABRP and ATG14 were significantly elevated in severe ICP patients. Moreover, GABRP was correlated with TBA (r = 0.64, p < 0.05), ATG14 (r = 0.87, p < 0.05), direct bilirubin (r = 0.54, p < 0.05), ALT (r = 0.72, p < 0.05), and AST (r = 0.67, p < 0.05). CONCLUSION: There were elevated expression of GABRP, ATG14 and LC3 in ICP placentas compared with uncomplicated pregnancies. The expression of GABRP was associated with autophagy and was correlated with the TBA levels.
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ABO blood group system is the most commonly used blood group classification system in clinic practice. The relevant antigens, A, B and H determinants, are complex carbohydrate molecules that are expressed in red blood cells and other cell lines and tissues. These antigens are determined by the ABO locus located on chromosome 9 (9q34.1-q34.2). ABO blood group is associated with the development of many human diseases, e.g., cardiovascular diseases, infectious diseases, and tumors. The relationship between the ABO blood group of pregnant women and various pregnancy complications, including preeclampsia (PE) and the related diseases, pregnancy associated venous thromboembolism (PA-VTE), gestational diabetes mellitus (GDM), and postpartum hemorrhage (PPH), have become the focus of obstetricians' recent research interest. Herein, we reviewed the relationship between ABO blood group and these pregnancy complications, and found that most of the reported findings supported the following views: 1) Blood type O is a protective factor for PE, while blood type AB increases the risk of PE; 2) blood types other than O are more prone to PA-VTE than blood type O; 3) blood type O or blood type AB may be related to the pathogenesis of GDM; 4) women of blood type O are at higher risks for PPH than those of other blood types. More in-depth epidemiological and genetic studies are needed to confirm these findings in the future. These findings can provide new ideas for researching into the pathogenesis of obstetric diseases and form the theoretical basis for obstetricians to prevent and treat related diseases.
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Diabetes Gestacional , Preeclampsia , Complicaciones del Embarazo , Tromboembolia Venosa , Sistema del Grupo Sanguíneo ABO/genética , Carbohidratos , Diabetes Gestacional/genética , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/etiología , Factores de Riesgo , Tromboembolia Venosa/complicacionesRESUMEN
The maternal-fetal interface is an essential environment for embryonic growth and development, and a successful pregnancy depends on the dynamic balance of the microenvironment at the maternal-fetal interface. Single-cell sequencing, which unlike bulk sequencing that provides averaged data, is a robust method for interpreting the cellular and molecular landscape at single-cell resolution. With the support of single-cell sequencing, the issue of maternal-fetal interface heterogeneity during pregnancy has been more deeply elaborated and understood, which is important for a deeper understanding of physiological and pathological pregnancy. In this paper, we analyze the recent studies of single-cell transcriptomics in the maternal-fetal interface, and provide new directions for understanding and treating various pathological pregnancies.
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Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy. Manifested with pruritus and elevation in bile acids, the etiology of ICP is still poorly understood. Although ICP is considered relatively benign for the mother, increased rates of adverse fetal outcomes including sudden fetal demise are possible devastating outcomes associated with ICP. Limited understanding of the underlying mechanisms restricted treatment options and managements of ICP. In recent decades, evolving evidence indicated the significance of autophagy in pregnancy and pregnancy complications. Autophagy is an ancient self-defense mechanism which is essential for cell survival, differentiation and development. Autophagy has pivotal roles in embryogenesis, implantation, and maintenance of pregnancy, and is involved in the orchestration of diverse physiological and pathological cellular responses in patients with pregnancy complications. Recent advances in these research fields provide tantalizing targets on autophagy to improve the care of pregnant women. This review summarizes recent advances in understanding autophagy in ICP and its possible roles in the causation and prevention of ICP.
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Autofagia/fisiología , Colestasis Intrahepática/fisiopatología , Complicaciones del Embarazo/fisiopatología , Animales , Ácidos y Sales Biliares/fisiología , Colestasis Intrahepática/complicaciones , Diabetes Gestacional , Estrés del Retículo Endoplásmico/fisiología , Femenino , Muerte Fetal , Retardo del Crecimiento Fetal , Humanos , Inmunidad , Inflamación , Preeclampsia , Embarazo , Especies Reactivas de Oxígeno/metabolismo , Factores de Riesgo , Ácido Ursodesoxicólico/fisiologíaRESUMEN
BACKGROUND: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. METHODS: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 µmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. FINDINGS: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35-3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04-2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86-1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39-0·91; p=0·016). INTERPRETATION: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. FUNDING: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.
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Colestasis Intrahepática/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico , Colagogos y Coleréticos/uso terapéutico , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: To assess the efficacy and safety of bilateral-contralateral cervix clamp firstly applied in postpartum hemorrhage caused by uterine tony of lower segment. METHODS: Totally 47 pregnant women with postpartum hemorrhage secondary to lower uterine segment atony in vaginal delivery or after caesarean delivery were included from March 1, 2020 to May 31, 2020. According to patient's informed consent, 22 women accepted cervical clamp to treat and 25 only used uterotonics in control group. Then hemostatic efficacy and safety of bilateral-contralateral cervix clamp were assessed by retrospective analysis. RESULTS: It was found that mean blood loss in clamp group was much less during vaginal delivery (656.2±72.79 g vs 811.8±86.07 g, p = 0.001) or after caesarean delivery (42.8±6.60 g vs 126.3±86.97 g, p = 0.007), and incidence of uterotonic repeated usage (81.8% vs 36, 18.2% vs 64%, p = 0.001) or side effect (18.2% vs 48.0%, p = 0.031) appeared less than control group, but there was no statistical differences on hospital stay (4.1±1.57 days vs 3.8±1.61 days, p = 0.535), hemoglobin (119±4.10 g vs 121.4±4.19 g, p = 0.058), blood transfusion (9.1% vs 12%,p = 0.746), surgical procedures (4.5% vs 4.0%, p = 0.93), also no clamp complications occurred. CONCLUSIONS: The bilateral-contralateral cervix clamp was effective and safe, this new technique could be a complementary treatment for postpartum hemorrhage.
Asunto(s)
Cuello del Útero , Parto Obstétrico , Hemorragia Posparto/cirugía , Instrumentos Quirúrgicos , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Atención Prenatal , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Both thyroid hormones and irisin have profound influences on the metabolism of the human body. Based on their similarities, several studies have been conducted to explore changes in irisin levels in patients with hypothyroidism and hyperthyroidism. This study was conducted in accordance with the PRISMA statement and the MOOSE reporting guideline. Based on a preregistered protocol (PROSPERO-CRD42019138430), a comprehensive search of eight databases was performed from inception to April 2020. Studies with original data collected from patients with thyroid dysfunction were included. Subgroup analysis was performed based on the different types of clinical manifestations and patient characteristics. The quality of each study and the presence of publication bias were assessed by the Newcastle-Ottawa score (NOS) and funnel plot with Egger's test, respectively. A total of 11 studies with 1210 participants were included. Ten studies were identified as high-quality studies. Pooled analysis indicated decreased irisin levels in patients with hypothyroidism (MD -10.37, 95% CI -17.81 to -2.93). Subgroup analysis revealed an even lower level of irisin in patients with clinical-type hypothyroidism (MD -17.03, 95% CI -30.58 to -3.49) and hypothyroidism caused by autoimmune disease (MD -19.38, 95% CI -36.50 to -2.26). No differences were found after achieving euthyroid status from levothyroxine treatment in patients with hypothyroidism compared with controls. No differences were found between patients with hyperthyroidism and controls. Correlation analyses revealed a possible negative correlation between irisin and TSH and positive correlations between irisin and both fT3 and fT4. Irisin was correlated with TSH receptor antibodies.