Spontaneous preterm birth prevention in multiple pregnancy

Multiple pregnancy is a major cause of spontaneous preterm birth, which is related to uterine overdistention. The objective of this study was to determine whether an oxytocin receptor antagonist, retosiban (GSK221149A), inhibited the procontractile effect of stretch on human myometrium. Myometrial biopsies were obtained at term planned cesarean delivery (n = 12). Each biopsy specimen was dissected into 8 strips that were exposed in pairs to low or high stretch (0.6 or 2.4 g) in the presence of retosiban (1 μM) or vehicle (dimethylsulfoxide) for 24 hours. Subsequently, we analyzed the contractile responses to KCl and oxytocin in the absence of retosiban. We found that incubation under high stretch in vehicle alone increased the response of myometrial explants to both KCl (P = .007) and oxytocin (P = .01). However, there was no statistically significant effect of stretch when explants were incubated with retosiban (P = .3 and .2, respectively). Incubation with retosiban in low stretch had no statistically significant effect on the response to either KCl or oxytocin (P = .8 and >.9, respectively). Incubation with retosiban in high stretch resulted in a statistically significant reduction (median fold change, interquartile range, P) in the response to both KCl (0.74, 0.60–1.03, P = .046) and oxytocin (0.71, 0.53–0.91, P = .008). The greater the effect of stretch on explants from a given patient, the greater was the inhibitory effect of retosiban (r = −0.65, P = .02 for KCl and r= −0.73, P = .007 for oxytocin). These results suggest that retosiban prevented stretch-induced stimulation of human myometrial contractility. Retosiban treatment is a potential approach for preventing preterm birth in multiple pregnancy.

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Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis

PLoS Medicine ◽

10.1371/journal.pmed.1003686 ◽

2021 ◽

Vol 18 (7) ◽

pp. e1003686

Author(s):

Sarah J. Stock ◽

Margaret Horne ◽

Merel Bruijn ◽

Helen White ◽

Kathleen A. Boyd ◽

...

Keyword(s):

Preterm Birth ◽

Prediction Model ◽

Risk Prediction ◽

Prospective Cohort ◽

Preterm Labour ◽

Meta Analysis ◽

Multiple Pregnancy ◽

Signs And Symptoms ◽

Risk Prediction Model ◽

Spontaneous Preterm Birth

Background Timely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness. Methods and findings Pregnant women included in the analyses were 22+0 to 34+6 weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an individual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016; 1,783 women; mean age 29.7 years; median BMI 24.8 kg/m2; 67.6% White; 11.7% smokers; 51.8% nulliparous; 10.4% with multiple pregnancy; 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018; 2,924 women; mean age 28.2 years; median BMI 25.4 kg/m2; 88.2% White; 21% smokers; 35.2% nulliparous; 3.5% with multiple pregnancy; 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R2 was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R2 of 36% (95% CI: 34% to 38%). Recalibration of the model’s intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than “treat all” or “treat none” strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset. Conclusions In this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice. Trial registration The study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry (ISRCTN 41598423) and NIHR Portfolio (CPMS: 31277).

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Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy

Cochrane Database of Systematic Reviews ◽

10.1002/14651858.cd012024.pub2 ◽

2017 ◽

Cited By ~ 4

Author(s):

Jodie M Dodd ◽

Rosalie M Grivell ◽

Cecelia M OBrien ◽

Therese Dowswell ◽

Andrea R Deussen

Keyword(s):

Preterm Birth ◽

Multiple Pregnancy ◽

Spontaneous Preterm Birth

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Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study

PLoS Medicine ◽

10.1371/journal.pmed.1003857 ◽

2021 ◽

Vol 18 (11) ◽

pp. e1003857

Author(s):

Sylvie Epelboin ◽

Julie Labrosse ◽

Jacques De Mouzon ◽

Patricia Fauque ◽

Marie-José Gervoise-Boyer ◽

...

Keyword(s):

Preterm Birth ◽

Pregnant Women ◽

Gestational Hypertension ◽

Multiple Pregnancy ◽

Fetal Distress ◽

Spontaneous Preterm Birth ◽

Multivariable Logistic Regression Model ◽

Assisted Reproductive Technique ◽

Obstetrical Outcomes ◽

Venous Thromboembolic Events

Background To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic. Methods and findings We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28). When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected. Conclusions We observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

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“Relaxin-dependent” way of implementing spontaneous preterm labor in multiple pregnancies: The involvement of placental relaxin 2

Journal of obstetrics and women s diseases ◽

10.17816/jowd60946 ◽

2021 ◽

Vol 70 (2) ◽

pp. 27-36

Author(s):

Olga V. Pachuliya ◽

Olesya N. Bespalova ◽

Mariya G. Butenko ◽

Yulia P. Milyutina ◽

Tatyana G. Tral ◽

...

Keyword(s):

Preterm Birth ◽

Histological Examination ◽

Preterm Labor ◽

Multiple Pregnancy ◽

Chorionic Villus ◽

Multiple Pregnancies ◽

Spontaneous Preterm Birth ◽

Wide Range ◽

Relaxin 2 ◽

Term Labor

BACKGROUND: Despite numerous studies, the etiopathogenesis of preterm birth in multiple pregnancy remains unclear, which determines the low effectiveness of measures for the prevention of preterm birth. This fact makes it necessary to study possible ways of implementing preterm birth in multiple pregnancies and to search for new biomarkers of their pathogenetic links. Experimental and clinical studies have demonstrated the contribution of the pleiotropic hormone relaxin to the regulation of a wide range of physiological processes and its role in the implementation of the pathogenetic mechanisms of pregnancy complications, primarily premature birth. The proven autocrine / paracrine mechanism of placental relaxin action, which implements important local effects, determines the prospects for studying the contribution of its dysregulation to the implementation of spontaneous preterm labor in multiple pregnancies. MATERIALS AND METHODS: A morphological examination of 92 placentas from 46 deliveries of dichorionic diamniotic twins was performed: 24 of them were spontaneous premature births and 22 spontaneous term births. Histological examination of placentas along with immunohistochemical verification of relaxin 2 expression in the chorionic villus of the dichorial twins placentas were carried out. RESULTS: Histological examination of the dichorionic twins placentas revealed that those from spontaneous preterm birth were characterized by a higher frequency of chronic placental insufficiency with reduced compensatory and adaptive mechanisms and more pronounced circulatory disorders in the circulatory bed of the villous tree, when compared to placentas from spontaneous term labor. The first verification of relaxin 2 expression in the chorionic villi of the dichorionic twins placenta showed the role of the peptide in the initiation of spontaneous preterm birth. The relative area of relaxin 2 expression in spontaneous preterm labor was significantly higher (p 0.05) compared to that in spontaneous term labor. CONCLUSIONS: The data obtained confirm the hypothesis put forward about the involvement of placental relaxin in the pathogenesis of spontaneous preterm labor in multiple pregnancies. The authors were the first to propose the definition of a relaxin-dependent way of implementing spontaneous preterm labor. To help define new preventive strategies, the prospects for further studies of the role and significance of relaxin in the implementation of pathogenic processes involved in spontaneous preterm birth in multiple pregnancies have been outlined.

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