Cytokines and the Risk of Preterm Delivery in Twin Pregnancies

Rode, Line; Klein, Katharina; Larsen, Helle; Holmskov, A; Andreasen, Kirsten Riis; Uldbjerg, Niels; Ramb, Jan; Bødker, Birgit; Skibsted, Lillian; Sperling, L.; Hinterberger, S; Krebs, Lone; Zingenberg, Helle; Weiss, Eva-Christine; Strobl, I; Laursen, L. C.; Christensen, Jeanette Tranberg; Skogstrand, Kristin; Hougaard, David M.; Krampl-Bettelheim, Elisabeth; Rosthøj, Susanne; Vogel, Ida; Tabor, Ann

doi:10.1097/aog.0b013e31825bc3cd

Cited by 18 publications

(27 citation statements)

References 40 publications

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“…137 We analyzed 2 studies that evaluated the predictive accuracy of cytokines for spontaneous preterm birth in twin gestations. 138,139 A cohort study assessed the ability of interleukin (IL)-1α, IL-6, and IL-8 concentrations in cervicovaginal secretions at 24–34 weeks to predict spontaneous preterm birth in 101 women with twin gestations. 138 IL-8, but not IL-1α or IL-6, was associated with a significant increase in the risk of spontaneous preterm birth at <37 weeks of gestation.…”

Section: Biochemical Testsmentioning

confidence: 99%

“…Recently, a secondary analysis of a randomized placebo-controlled trial investigating the preventive effect of vaginal progesterone on the risk of preterm delivery in diamniotic twin gestations reported on the association between cytokine levels in dried blood spots and the risk of spontaneous preterm birth in twin gestations. 139 Concentrations of 24 inflammatory markers were measured upon enrollment into the study (18–25 weeks of gestation) and after 4–8 weeks of treatment. Among women in the placebo group (n = 265), only levels of IL-8 in the second blood sample were significantly increased in spontaneous deliveries <34 weeks of gestation compared with term deliveries ( P <.001).…”

Section: Biochemical Testsmentioning

confidence: 99%

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Prediction of preterm birth in twin gestations using biophysical and biochemical tests

Conde-Agudelo

Romero

2014

American Journal of Obstetrics and Gynecology

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The objective of this study was to determine the performance of biophysical and biochemical tests for the prediction of preterm birth in both asymptomatic and symptomatic women with twin gestations. We identified a total of 19 tests proposed to predict preterm birth, mainly in asymptomatic women. In these women, a single measurement of cervical length with transvaginal ultrasound before 25 weeks of gestation appears to be a good test to predict preterm birth. Its clinical potential is enhanced by the evidence that vaginal progesterone administration in asymptomatic women with twin gestations and a short cervix reduces neonatal morbidity and mortality associated with spontaneous preterm delivery. Other tests proposed for the early identification of asymptomatic women at increased risk of preterm birth showed minimal to moderate predictive accuracy. None of the tests evaluated in this review meet the criteria to be considered clinically useful to predict preterm birth among patients with an episode of preterm labor. However, a negative cervicovaginal fetal fibronectin test could be useful in identifying women who are not at risk for delivering within the next week, which could avoid unnecessary hospitalization and treatment. This review underscores the need to develop accurate tests for predicting preterm birth in twin gestations. Moreover, the use of interventions in these patients based on test results should be associated with the improvement of perinatal outcomes.

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Section: Biochemical Testsmentioning

confidence: 99%

Section: Biochemical Testsmentioning

confidence: 99%

Prediction of preterm birth in twin gestations using biophysical and biochemical tests

Conde-Agudelo

Romero

2014

American Journal of Obstetrics and Gynecology

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“…Several epidemiological studies demonstrate that proinflammatory cytokines, such as TNF-a, and chemokines, such as IL-8, are associated with adverse pregnant outcomes including preterm delivery and fetal growth restriction (15,16). Numerous animal experiments indicate that proinflammatory cytokines, such as TNF-a, contribute to LPS-induced fetal demise, NTDs, and intrauterine growth restriction (IUGR) (7,8,11,17).…”

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confidence: 99%

Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and Intrauterine Growth Restriction through Its Anti-Inflammatory Activity

Chen

Zhou

et al. 2016

The Journal of Immunology

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Farnesoid X receptor (FXR) is expressed in human and rodent placentas. Nevertheless, its function remains obscure. This study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal death and intrauterine growth restriction. All pregnant mice except controls were i.p. injected with LPS (100 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to GD17. As expected, placental FXR signaling was activated by OCA. OCA pretreatment protected against LPS-induced fetal death. In addition, OCA pretreatment alleviated LPS-induced reduction of fetal weight and crown-rump length. Additional experiments showed that OCA inhibited LPS-evoked TNF-α in maternal serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced upregulation of placental proinflammatory genes including Tnf-α, Il-1β, IL-6, Il-12, Mip-2, Kc, and Mcp-1 By contrast, OCA elevated anti-inflammatory cytokine IL-10 in maternal serum, amniotic fluid, and placenta. Further analysis showed that OCA blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth zone. These results provide a mechanistic explanation for placental FXR-mediated anti-inflammatory activity. Overall, this study provides evidence for roles of FXR as an important regulator of placental inflammation.

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“…Numerous animal experiments have demonstrated that proinflammatory cytokines and chemokines are associated with LPS-induced fetal death, preterm delivery, and IUGR [ 20 , 21 ]. Therefore, we investigated the effect of ADL extract pretreatment on LPS-induced cytokine and chemokine expression in placental tissues.…”

Section: Resultsmentioning

confidence: 99%

Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α

Kim

Kang

et al. 2020

Molecules

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Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

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Cytokines and the Risk of Preterm Delivery in Twin Pregnancies

Abstract: Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels.

Cited by 18 publications

References 40 publications

Prediction of preterm birth in twin gestations using biophysical and biochemical tests

Prediction of preterm birth in twin gestations using biophysical and biochemical tests

Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and Intrauterine Growth Restriction through Its Anti-Inflammatory Activity

Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α

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