Preterm Birth In Multiple Pregnancies Research Articles

Преждевременные роды при многоплодной беременности после ЭКО с использованием аутологичных и донорских ооцитов

Objective. To analyze the rate and pattern of preterm birth in multiple pregnancy after in vitro fertilization (IVF) using donor and autologous oocytes. Patients and methods. The rate of preterm birth in 213 women with a dichorionic diamniotic twin pregnancy was analyzed. All patients were divided into three groups: IVF-DO – 68 women who became pregnant after IVF with donor oocytes, IVF-AO – 73 women who became pregnant after IVF with autologous oocytes, and NTP – 72 women with natural twin pregnancy. The study included only those women whose pregnancy resulted in birth. Results. Most of the patients in the IVF-DO group were over 40 years of age, while the other groups were dominated by women under 35 years of age. There was no statistically significant increase in the overall rate of preterm birth in the IVF groups compared to the NTP group. However, pregnancy termination before 34 weeks’ gestation was significantly more frequent in patients in the IVF-DO group (OR = 3.28; 95% CI = 0.99–10.86). There were also significantly higher rates of pregnancy complications such as pre-eclampsia (PE) (OR = 10.42; 95% CI = 2.94–36.94), gestational hypertension (GH) (OR = 11.16; 95% CI = 3.16–39.43), intrahepatic cholestasis of pregnancy (ICP) (OR = 4.67; 95% CI = 0.95–22.82), and placental abruption (PA) (OR = 9.47; 95% CI = 1.15–77.86) in the IVF-DO group. Conclusion. Multiple pregnancy after IVF with donor oocytes include a combination of several significant and age-independent risk factors for preterm birth. Key words: preterm birth, IVF, oocyte donation, multiple pregnancy, twins

Working conditions in women with multiple pregnancy—the impact on preterm birth and adherence to guidelines: a prospective cohort study

Women with multiple pregnancies are at risk for maternal complications such as preterm birth. Hazardous working conditions, such as physically demanding work and long and irregular working hours, might increase the risk of preterm birth. This study primarily aimed to determine whether certain working conditions up to 20 weeks of pregnancy increase the risk of preterm birth in multiple pregnancies. The secondary objective was to evaluate whether the working conditions of Dutch women with multiple pregnancy have been adjusted to the guidelines of the Netherlands Society of Occupational Medicine. We performed a prospective cohort study alongside the ProTWIN trial, a multicenter randomized controlled trial that assessed whether cervical pessaries could effectively prevent preterm birth. Women with paid work of >8 hours per week completed questionnaires concerning general health and working conditions between 16 and 20 weeks of pregnancy. Univariable and multivariable logistic regression analyses were performed to identify work-related factors associated with preterm birth (32-36 weeks' gestation) and very preterm birth (<32 weeks' gestation). We analyzed a subgroup of participants who worked for more than half of the week (>28 hours). We calculated the proportion of women who reported work-related factors not in accordance with guidelines. We studied 383 women, of whom 168 (44%) had been randomized to pessary, 142 (37%) to care as usual, and 73 (19%) did not participate in the randomized part of the study. After adjusting for confounding variables, working >28 hours was associated with very preterm birth (n=33; 78%) (adjusted odds ratio, 3.0; 95% confidence interval, 1.1-8.1), and irregular working times were associated with preterm birth (n=26, 17%) (adjusted odds ratio, 2.0; 95% confidence interval, 1.0-4.1) and very preterm birth (n=10; 24%) (adjusted odds ratio, 2.7; 95% confidence interval, 1.0-7.3). Within a subgroup of 213 participants working >28 hours per week, multivariable analysis showed that irregular working times (n=16; 20%) (adjusted odds ratio, 3.5; 95% confidence interval, 1.2-10.1) and no/little freedom in performance of tasks (n=23; 28%) (adjusted odds ratio, 3.0; 95% confidence interval, 1.3-7.3) were associated with preterm birth. Irregular working times (n=9; 27%) (adjusted odds ratio, 3.4; 95% confidence interval, 1.0-11.1), requiring physical strength (n=9; 27%) (adjusted odds ratio, 5.3; 95% confidence interval, 1.6-17.8), high physical workload (n=7; 21%) (adjusted odds ratio, 3.9; 95% confidence interval, 1.1-13.9), and no/little freedom in performing tasks (n=10; 30%) (adjusted odds ratio, 3.2; 95% confidence interval, 1.1-9.6) were associated with very preterm birth. Before 20 weeks of pregnancy, 224 (58.5%) women with multiple pregnancy continued to work under circumstances that were not in accordance with the guidelines. In our cohort study, nearly 60% of women with multiple pregnancy continued to work under circumstances not in accordance with the guidelines to avoid physical and job strain and long and irregular working hours. Irregular hours were associated with preterm and very preterm birth, and long hours were associated with preterm birth.

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

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.&#x0D; 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.&#x0D; 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.&#x0D; 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.

Integral assessment of markers of the local infectious and inflammatory process in women with preterm birth in multiple pregnancies

Hypothesis/Aims of study. Premature birth in multiple pregnancies remains an important object of research, since it is the main factor in poor perinatal outcomes, and their heterogeneous mechanisms determine the ineffectiveness of prediction and prevention methods. In the pathogenesis of premature birth, as is known, one of the leading links is inflammation caused by infections of the lower genital tract (40%). In multiple pregnancies, which in most cases occur as a result of assisted reproductive technology treatment (70%) and are mainly accompanied by complications, pregravid preparation and antenatal observation include more careful control and correction of local infectious and inflammatory processes. In this regard, the persisting high rate of premature birth in multiple pregnancies (about 54%) demonstrates the ambiguity of the opinion about the suppressive role of the infectious factor in the induction of premature birth and determines the need for studying its contribution to multifactorial genesis. The aim of this study was to conduct an integral assessment of markers of the local infectious and inflammatory process in women with PB in multiple pregnancies.&#x0D; Study design, materials and methods. We performed a comprehensive study of the bacteriological composition of the lower genital tract discharge using microscopic, bacteriological, and molecular biological methods (Femoflor 16 test) and assessed the local inflammatory status (ImmunoQuantex test) in 30 pregnant women with dichorionic diamniotic twins. The main group consisted of women with premature birth (n = 13), the control group comprising those with term birth (n = 16), while patients with induced premature birth (n = 2) were not included in the comparative analysis.&#x0D; Results. This study was the first to determine the features of vaginal microbiocenosis and the local immune status in women with premature birth in multiple pregnancies. In general, the study cohort had a low inflammatory status and normal or intermediate types of vaginal biotope. The most common disruptions (24.1%) were vaginal dysbiosis, expressed in a small amount of Lactobacillius spp., and non-specific vaginitis associated with Mycoplasma hominis. The local immune status of women with premature birth was characterized by a relative decrease in the mRNA expression of such innate immunity genes as IL1B, TNF, TLR4, and GATA3. An integrated assessment of the studied parameters based on the data obtained allowed us to build a mathematical model for predicting premature birth with the probability of 87.6%.&#x0D; Conclusion. The integral assessment of infectious and inflammatory markers is important from the standpoint of not only their possible identification as predictors, but also a general understanding of the genesis of premature birth.

The effect of early administration of rectal progesterone in IVF/ICSI twin pregnancies on the preterm birth rate: a randomized trial

BackgroundThe rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11–14 weeks for prevention of preterm birth.MethodsThis is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome.ResultsA total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks.ConclusionsRectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth.Trial registrationThe trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120.

Многофакторное прогнозирование реализации преждевременных родов при многоплодии

Многофакторное прогнозирование реализации преждевременных родов при многоплодии

Prevention and therapy of threatened preterm birth in multiple pregnancy

Preterm birth in multiple pregnancy is an important medical, economic and social problem. Currently, more than half of twins are born prematurely, which puts them at high risk of developing neonatal diseases causing lifelong disability and social maladjustment. In this regard, reducing the frequency of preterm multiple births is an important task of modern obstetrics. Improving perinatal outcomes of multiple pregnancies can only be achieved using the most effective measures that have a good evidence base. At the same time, numerous studies on the effectiveness of therapeutic interventions aimed at prolonging multiple pregnancies have reported contradictory results. This review included most of the randomized controlled trials of methods for the prevention and treatment of threatening preterm birth in multiple pregnancies, as available in PubMed, Google Academy, Elibrary, and the Cochrane Central Register of Controlled Trials. Thus far, studies on the use of bed rest, prophylactic tocolysis, most of the progestins, and cervical cerclage in multiple pregnancy have shown no efficacy in reducing the risk of premature birth. However, encouraging data were obtained on improving neonatal outcomes of multiple pregnancies using vaginal progesterone and an obstetric pessary, but these results require additional confirmation in larger multicenter randomized studies. Further clinical trials are needed to develop algorithms for timely diagnosis and adequate treatment of threatened preterm birth in case of multiple pregnancy, including the use of the most rational preventive and therapeutic methods that have a high evidence level.

Spontaneous preterm birth prevention in multiplepregnancy.

Key content Twin pregnancies are associated with a three‐fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation.The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons.Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm.The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies.There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply. Learning objectives To review the burden of preterm birth in multiple pregnancy.To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one.To be aware of the use of the Arabin pessary.

Immunohistochemical features of progesterone receptors expression of placental barrier in women with multiple pregnancies resulting from assisted reproduction

Hormonal disorders are one of the main known causes of miscarriage and preterm birth in multiple pregnancies resulting from assisted reproductive technology (ART). Progesterone and the number of its receptors play an important role in the preservation and prolongation of pregnancy and it is the pressing issue of our time. The study of placentas, as the main site of synthesis of progesterone, has high informative potential and it is the most important diagnostic object, and information received by its research is essential for the full conclusion on the causes, mechanisms, close and long-term effects of multiple pregnancy pathology. Aim. The aim of our study was to investigate immunohistochemical features of placentas from women with dichorionic diamniotic twin pregnancies in spontaneous fertilization and after use of assisted reproductive technology (ART). Methods and results. According to this goal we examined 94 women, 44 of whom had multiple pregnancies due to ART, 42 with separate multiple pregnancy and 38 women with a singleton pregnancy. We carried out clinical and statistical analysis of the course of pregnancy and childbirth in the studied groups. During the study it was found that multiple pregnancies due to assisted reproduction belong to the high risk of gestation, at which premature births occur much more frequently than in singleton pregnancies. We were the first to carry out the immunohistochemical study of placentas in which the highest expression of progesterone receptors in the nuclei of cells of decidua (45%) related to the parent structure of the placenta from women with multiple pregnancies caused by ART is found. It is also found that with increasing gestational age, there has been a significant decrease in the expression of the activity of progesterone receptors (from 45 to 2.5%), regardless of the method of conception and the number of fetuses. Conclusions. The results of the study point to the definitive link of structures of placental-endometrial relations as an important component of the appropriateness of hormone therapy.

Pessary Placement in the Prevention of Preterm Birth in Multiple Pregnancies

Preterm birth is the major contributor to perinatal mortality and serious neonatal morbidity, and approximately 30% of all patients admitted to a neonatal intensive care unit in the Netherlands are born from a multiple pregnancy. In asymptomatic women with a multiple pregnancy and short cervix, prophylactic use of a cervical pessary might reduce preterm birth. The aim of this study is to assess the possible treatment effects of pessary use in pregnancy duration and for poor perinatal outcome. This cohort study was performed between December 2012 and September 2014 in 44 hospitals in the Netherlands. Cervical length was measured between 16 and 22 weeks of gestation. When cervical length was below 38 mm, women were offered a cervical pessary. The pessaries were removed at 36 weeks of gestation or in case of premature rupture of the membranes, active vaginal bleeding, other signs of preterm labor, or severe patient discomfort. The course of pregnancy, including perinatal outcome in these women, was compared with the outcome of women from the placebo group of the AMPHIA trial (ISRCTN40512715) (historical cohort). Propensity score matching with replacement was used to create comparable baseline characteristics between both populations. The study included 63 women in the pessary group and 56 women as control subjects. Propensity score matching generated 57 women in the intervention group matched to 57 women (31 unique) in the control group. Gestational age at delivery was comparable between both groups (hazard ratio, 0.96; 95% confidence interval [CI], 0.46–1.46), as well as their delivery rates before 28, 32, and 37 weeks (RR, 0.68 [95% CI, 0.21–2.18]; RR, 0.54 [95% CI, 0.21–1.41]; and RR, 1.22 [95% CI, 0.47–3.15]), respectively. There was no difference in composite perinatal outcome (RR, 1.36 [95% CI, 0.53–3.51]) and perinatal mortality (RR, 0.89 [95% CI, 0.24–3.38]) either. Results of this cohort study with propensity score analysis could not confirm the positive effect of pessary therapy in the prevention of preterm birth in asymptomatic multiple pregnancies with a short cervix in this propensity score analysis. With ongoing studies on this subject, the definite answer whether pessaries are effective in the prevention of preterm birth will come. If effective, evaluation of implementation, similar to this study, is still necessary.

Pessary placement in the prevention of preterm birth in multiple pregnancies: a propensity score analysis

ObjectiveIn asymptomatic women with a multiple pregnancy and short cervix prophylactic use of a cervical pessary might reduce preterm birth. We assessed the possible treatment effects of pessary use in pregnancy duration and for poor perinatal outcome. Study designThis cohort study was performed between December 2012 and September 2014 in 44 hospitals in the Netherlands. Women with multiple pregnancy had a cervical length measurement between 16 and 22 weeks of gestation. When cervical length was below 38mm, women were offered a cervical pessary. The course of pregnancy, including perinatal outcome in these women was compared to the outcome of women from the placebo group of the AMPHIA trial (ISRCTN40512715) (historical cohort). Propensity-score matching with replacement was used to create comparable baseline characteristics between both populations. ResultsWe studied 63 women in the pessary group and 56 women as controls. Propensity-score matching generated 57 women in the intervention group matched to 57 women (31 unique) in the control group. Gestational age at delivery was comparable between both groups (HR 0.96, 95%-CI 0.46–1.46) as well as their delivery rates before 28, 32 and 37 weeks, RR 0.68 (95%-CI 0.21–2.18), RR 0.54 (95%-CI 0.21–1.41), and RR 1.22 (95%-CI 0.47–3.15), respectively. There was no difference in composite perinatal outcome (RR 1.36, 95%-CI 0.53–3.51) and perinatal mortality (RR 0.89, 95%-CI 0.24–3.38) either. ConclusionIn this cohort study with propensity score analysis, pessary use did not prevent preterm birth in asymptomatic women with a multiple pregnancy and short cervix.

The Effect of an Oxytocin Receptor Antagonist (Retosiban, GSK221149A) on the Response of Human Myometrial Explants to Prolonged Mechanical Stretch.

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.

Cervical stitch (cerclage) for preventing preterm birth in multiple pregnancy.

Cervical cerclage is a surgical intervention involving placing a stitch around the uterine cervix. The suture material aims to prevent cervical shortening and opening, thereby reducing the risk of preterm birth. The effectiveness and safety of this procedure in multiple gestations remains controversial. To assess whether the use of a cervical cerclage in multiple gestations, either at high risk of pregnancy loss based on just the multiple gestation (history-indicated cerclage), the ultrasound findings of 'short cervix' (ultrasound-indicated cerclage), or the physical exam changes in the cervix (physical exam-indicated cerclage), improves obstetrical and perinatal outcomes. The primary outcomes assessed were perinatal deaths, serious neonatal morbidity, and perinatal deaths and serious neonatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2014) and reference lists of retrieved studies. All randomised controlled trials (RCTs) of cervical cerclage in multiple pregnancies. Quasi-RCTs and RCTs using a cluster-randomised design were eligible for inclusion (but none were identified). Studies using a cross-over design and those presented only as abstracts were not eligible for inclusion.We included studies comparing cervical cerclage with no cervical cerclage in multiple pregnancies.Studies comparing cervical stitch versus any other preventative therapy (e.g. progesterone) in multiple pregnancies, and studies involving comparisons between different cerclage protocols (history-indicated versus ultrasound-indicated versus physical exam-indicated cerclage) were also eligible for inclusion but none were identified. Two review authors independently assessed trials for inclusion and risk of bias. Two review authors extracted data. Data were checked for accuracy. We included five trials, which in total randomised 1577 women, encompassing both singleton and multiple gestations. After excluding singletons, the final analysis included 128 women, of which 122 women had twin gestations, and six women had triplet gestations. Two trials (n = 73 women) assessed history-indicated cerclage, while three trials (n = 55 women) assessed ultrasound-indicated cerclage. The five trials were judged to be of average to above average quality, with three of the trials at unclear risk regarding selection and detection biases.Concerning the primary outcomes, when outcomes for cerclage were pooled together for all indications and compared with no cerclage, there was no statistically significant differences in perinatal deaths (19.2% versus 9.5%; risk ratio (RR) 1.74, 95% confidence intervals (CI) 0.92 to 3.28, five trials, n = 262), serious neonatal morbidity (15.8% versus 13.6%; average RR 0.96, 95% CI 0.13 to 7.10, three trials, n = 116), or composite perinatal death and neonatal morbidity (40.4% versus 20.3%; average RR 1.54, 95% CI 0.58 to 4.11, three trials, n = 116).Among the secondary outcomes, there were no significant differences between the cerclage and the no cerclage groups. To name a few, there were no significant differences among the following: preterm birth less than 34 weeks (average RR 1.16, 95% CI 0.44 to 3.06, four trials, n = 83), preterm birth less than 35 weeks (average RR 1.11, 95% CI 0.58 to 2.14, four trials, n = 83), low birthweight less than 2500 g (average RR 1.10, 95% CI 0.82 to 1.48, four trials, n = 172), very low birthweight less than 1500 g (average RR 1.42, 95% CI 0.52 to 3.85, four trials, n = 172), and respiratory distress syndrome (average RR 1.70, 95% CI 0.15 to 18.77, three trials, n = 116). There were also no significant differences between the cerclage and no cerclage groups when examining caesarean section (elective and emergency) (RR 1.24, 95% CI 0.65 to 2.35, three trials, n = 77) and maternal side-effects (RR 3.92, 95% CI 0.17 to 88.67, one trial, n = 28).Examining the differences between prespecified subgroups, ultrasound-indicated cerclage was associated with an increased risk of low birthweight (average RR 1.39, 95% CI 1.06 to 1.83, Tau² = 0.01, I² = 15%, three trials, n = 98), very low birthweight (average RR 3.31, 95% CI 1.58 to 6.91, Tau² = 0, I² = 0%, three trials, n = 98), and respiratory distress syndrome (average RR 5.07, 95% CI 1.75 to 14.70, Tau² = 0, I² = 0%, three trials, n = 98). However, given the low number of trials, as well as substantial heterogeneity and subgroup differences, these data must be interpreted cautiously.No trials reported on long-term infant neurodevelopmental outcomes. There were no physical exam-indicated cerclages available for comparison among the studies included. This review is based on limited data from five small studies of average to above average quality. For multiple gestations, there is no evidence that cerclage is an effective intervention for preventing preterm births and reducing perinatal deaths or neonatal morbidity.

Prediction of Preterm Birth in Multiple Pregnancies: Development of a Multivariable Model Including Cervical Length Measurement at 16 to 21 Weeks’ Gestation

ObjectiveTo develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks’ gestation and other variables. MethodsWe used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks’ gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures. ResultsWe studied 507 women, of whom 270 (53%) delivered<37 weeks (preterm) and 66 (13%)<32 weeks (very preterm). Women with cervical length<30mm delivered more often preterm (hazard ratio 1.9; 95% CI 0.7 to 4.8). Other independently contributing predictors were previous preterm delivery, monochorionicity, smoking, educational level, and triplet pregnancy. Prediction models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration. ConclusionIn women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

Put a Ring on It? Pessaries for Preventing Preterm Birth in Multiple Pregnancies

Preterm birth results in a high burden of morbidity and mortality worldwide; moreover, effective interventions to lower risk for early delivery

Preterm birth in multiple pregnancy: a glimmer of hope?

Preterm birth in multiple pregnancy: a glimmer of hope?

PF.02 The Role of Quantitative Fetal Fibronectin and Cervical Length in Predicting Spontaneous Preterm Birth in Multiple Pregnancies

BackgroundMultiple pregnancies are associated with a higher risk of spontaneous preterm birth (sPTB). Whilst fetal fibronectin (fFN) and cervical length (CL) measurement can predict sPTB in singleton pregnancies (Kurtzman et...

Effect of 17‐alpha hydroxyprogesterone caproate on cervical length in twin pregnancies

Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies. This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21). In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use.

Vaginal progesterone to prevent preterm birth in multiple pregnancy: a randomized controlled trial

We sought to assess the effect of progesterone in increasing or decreasing duration of pregnancy for mothers with twins and triplets. Women with multiple pregnancy were randomized at 16+0 to 20+6 weeks' gestation to receive daily doses of either 90 mg progesterone vaginal gel or placebo until 35+6 weeks or delivery. Primary outcome was gestational age (GA) at delivery. Secondary outcomes included preterm birth, infant morbidity and mortality, and adverse events up to 28 days after delivery. A sample size of 40 per group was required to detect a 2-week difference in GA at delivery. Eighty-four women were randomized (42 to progesterone, 42 to placebo). Median GA at delivery was 36+3 and 36+2, respectively (difference, 1 day; 95% confidence interval, 4 to -1 days, P=0.585). There were no clinically or statistically significant differences between groups for risk of delivery before 35 or 37 weeks' GA, rates of infant morbidity and mortality, treatment compliance, or adverse events. Daily treatment with progesterone gel did not prolong multiple pregnancy compared with placebo. Effective prevention strategies are needed to reduce preterm deliveries among women with multiple gestations.

Expression of gastrin‐releasing peptide is increased by prolonged stretch of human myometrium, and antagonists of its receptor inhibit contractility

Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. The aim of this study was to identify factors that mediate the effect of stretch on human myometrium.Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or a 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Tissue held at tonic stretch with the 2.4 g mass for either 24 or 65 h showed increased potassium chloride (KCl)-induced and oxytocin-induced contractility compared with that held with the 0.6 g mass. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP mRNA by stretch was confirmed in a separate series of 10 samples using quantitative RT-PCR (qRT-PCR) (2.8-fold, P =0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 2 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of a further 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h, respectively) significantly reduced KCl- and oxytocin-induced contractility.Tonic stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium with GRP receptor antagonists attenuates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy.