女性生殖系统微生物群落及其与早产相关性研究进展

女性生殖系统微生物群落与女性生殖健康密切相关。阴道微生物的菌群变化伴随着多种阴道疾病的发生并可能通过宫颈感染子宫,孕期子宫内的炎症反应会导致胎儿早产(Preterm Birth,PTB),PTB被定义为妊娠满28周但不足37周所发生的分娩现象,PTB婴儿死亡率很高并面临着多种健康疾病,除了明确病原微生物的感染,PTB还伴随着生殖系统微生物群落失衡,将来有望通过根据女性生殖系统微生物群落的动态变化来预防PTB的发生。本综述将着重介绍女性生殖系统微生物群落与生殖健康,尤其是与PTB之间的联系。     

Long noncoding RNA expression in the cervix mid-pregnancy is associated with the length of gestation at delivery

Infants born preterm are at increased risk of multiple morbidities and mortality. Why some women deliver preterm remains poorly understood. Prior studies have shown that cervical microRNA expression and DNA methylation are associated with the length of gestation. However, no study has examined the role of long noncoding RNAs (lncRNAs) in the cervix during pregnancy. To determine whether expression of lncRNAs is associated with length of gestation at delivery, we analyzed RNA from cervical swabs obtained from 78 women during pregnancy (mean 15.5, SD 5.0, weeks of gestation) who were participating in the Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) Study in Boston, MA, USA. We used a PCR-based platform and found that 9 lncRNAs were expressed in at least 50% of the participants. Of these, a doubling of the expression of TUG1, TINCR, and FALEC was associated with shorter lengths of gestation at delivery [2.8 (95% CI: 0.31, 5.2); 3.3 (0.22, 6.3); and 4.5 (7.3, 1.6) days shorter respectively]. Of the lncRNAs analyzed, none was statistically associated with preterm birth, but expression of FALEC was 2.6-fold higher in women who delivered preterm vs. term (P = 0.051). These findings demonstrate that lncRNAs can be measured in cervical samples obtained during pregnancy and are associated with subsequent length of gestation at delivery. Further, this study supports future work to replicate these findings in other cohorts and perform mechanistic studies to determine the role of lncRNAs in the cervix during pregnancy.     

三维能量多普勒超声鉴别宫颈过短孕妇先兆早产的作用研究

目的：使用三维能量多普勒超声比较先兆早产和无症状宫颈过短单胎孕妇的宫颈体积和血管指数。方法：预先扫描妊娠 24-34.6 周的300 例无症状健康孕妇的宫颈长度。将宫颈长度过短，小于孕周的10%的孕妇纳入无症状宫颈短组，测量该组孕妇宫 颈体积和血管指数（Ⅵ）、血管血流指数（VFI）和血流指数（FI）。先兆早产组患者入院的24 小时内测量同样的超声参数。记录孕妇 的体重指数、孕周、吸烟状况、经产状况、早产家族史、母亲为早产出生者以及之前的早产情况等数据。比较两组孕妇超声检查结 果和病史参数。结果：29 例无症状健康妇女（9.6%）宫颈较短。两组间的病史参数或宫颈长度无显著差异。先兆早产组的宫颈体积 较小（12.90 vs 17.168 cm3，P = 0.005）。无症状宫颈过短孕妇的VI 和VFI 均较低（VI：4.369% vs 15.939%，P<0.001；VFI：1.514 vs 4.878，P<0.001）。宫颈过短组的FI较高（33.581 vs 30.311，P=0.006）。结论：无症状宫颈过短组孕妇与先兆早产组孕妇之间的宫颈 长度类似，但两组间宫颈体积和血管指数存在差异。     

生物蛋白胶封堵合并宫颈环扎术治疗胎膜早破的疗效观察

目的:观察生物蛋白胶封堵合并宫颈环扎术治疗胎膜早破,对孕妇、胎儿及新生儿的影响,明确该技术治疗胎膜早破的疗效。方法:我院产科共收治妊娠<30周胎膜早破患者48例,采用生物蛋白胶封堵合并宫颈环扎术治疗胎膜早破,观察治疗后孕妇羊水指数,胎儿双顶径,新生儿出生时体重,及孕妇的副反应。结果:在本次封堵治疗过程中均一次封堵成功,没有不良反应发生,所有孕妇术后阴道流水情况均明显改善,其中有2例孕妇术后1周阴道流水停止。所有孕妇术后羊水漏出量均明显减少,B超检查显示羊水指数均在(6±2)cm,胎儿每周双顶径增长均达到(0.15±0.02)cm,延长孕周最短(5±2)w,10例早产,38例继续妊娠至37 w。新生儿出生时体重为(2000±260)g,无1例发生NRDS。同期没有进行宫颈内封堵仅行药物保胎治疗的10例孕妇,胎龄延长最长达到10 d,最短者24 h内出现早产分娩,早产儿平均体重1400 g,均发生NRDS,有2例放弃治疗,4例在NICU行治疗,最终因各种并发症死亡。48例行封堵治疗孕妇未发生过敏反应,无阴道出血及产后出血和感染等。结论:应用生物蛋白胶结合宫颈环扎术治疗胎膜早破,手术操作简单,可延长了孕周,提高了新生儿成活率,无不良反应,具有广泛的应用前景。     

Macrophage trafficking in the uterus and cervix precedes parturition in the mouse.

Immune activation is implicated in the etiology of preterm labor, but little is known about macrophage number or distribution in the uterus or cervix at term. This study tested the hypothesis that macrophages migrate into the reproductive tract before the onset of parturition. Paraffin-embedded sections from the mid-uterine horn and cervix of C3/HeN mice on Days 15 and 18 of pregnancy, the day of birth (Day 19), and 1 day postpartum were stained with a pan-macrophage marker to analyze cell numbers and distribution. During pregnancy, uterine macrophages were dispersed in endometrium, usually associated with vasculature and subluminal epithelium. In myometrium, macrophages were clustered in stromal connective tissue; near term and postpartum, cells appeared to surround the muscle bundles. Total macrophage numbers were increased on Day 15 relative to those in nonpregnant controls, declined before birth, and increased postpartum. In the cervix, macrophages congregated in subepithelium, often perivascular or near ganglia. Macrophage numbers in the cervix peaked on Day 18, then declined to nonpregnant levels by the day after birth. Thus, macrophage numbers in the uterus were inversely related to those in the cervix. These findings raise the possibility that macrophages and their products may be involved in uterine contractility and cervical remodeling during the processes of parturition.     

Cervical Mucus Properties Stratify Risk for Preterm Birth

Background

Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth.

Methods and Findings

To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus.

Conclusions

Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.     

择期经阴道宫颈环扎术与期待疗法治疗宫颈机能不全的效果比较

目的:比较择期经阴道宫颈环扎术以及期待疗法治疗宫颈机能不全的效果。方法:选择2017年10月~2019年10月我院收治的201例宫颈机能不全患者,将其随机分为两组。对照组100例患者采取期待疗法,即卧床休息,口服地屈孕酮,每次服用的剂量为10 mg,每日2次,一直服药到30孕周;观察组101例患者择期经阴道宫颈环扎术,比较两组的早产率、成功妊娠率、新生儿出生体重以及分娩孕周。结果:对照组100例宫颈机能不全患者中,22例患者流产(占22.00%),78例患者获得活婴(占78.00%),78例成功分娩的患者中,47例患者≥37周分娩,31例患者<37周分娩,早产率为39.74%(31/78)。观察组的101例患者中,8例患者流产(占7.92%),93例患者获得活婴(占92.08%)。93例成功分娩的患者中,81例患者≥37周分娩,12例患者<37周分娩,早产率为12.90%(12/93);12例早产的患者中,4例患者由于胎膜早破和胎儿窘迫,而在孕32~33周采取剖宫产手术,2例患者由于胎膜早破臀位,而在孕35~36周时采取剖宫产手术,6例患者在孕35~36周早产。观察组宫颈机能不全患者的早产率明显低于对照组(P<0.05),且成功妊娠率、新生儿出生体重以及分娩孕周明显高于或长于对照组(P<0.05)。结论:与期待疗法相比较,择期经阴道宫颈环扎术不但可以明显延长宫颈机能不全患者的分娩孕周,提高成功妊娠率,还能改善新生儿的预后、降低早产的风险。     

Biaxial biomechanical properties of the nonpregnant murine cervix and uterus

From a biomechanical perspective, female reproductive health is an understudied area of research. There is an incomplete understanding of the complex function and interaction between the cervix and uterus. This, in part, is due to the limited research into multiaxial biomechanical functions and geometry of these organs. Knowledge of the biomechanical function and interaction between these organs may elucidate etiologies of conditions such as preterm birth. Therefore, the objective of this study was to quantify the multiaxial biomechanical properties of the murine cervix and uterus using a biaxial testing set-up. To accomplish this, an inflation-extension testing protocol (n = 15) was leveraged to quantify biaxial biomechanical properties while preserving native matrix interactions and geometry. Ultrasound imaging and histology (n = 10) were performed to evaluate regional geometry and microstructure, respectively. Histological analysis identified a statistically significant greater collagen content and significantly smaller smooth muscle content in the cervix as compared to the uterus. No statistically significant differences in elastic fibers were identified. Analysis of bilinear fits revealed a significantly stiffer response from the circumferentially orientated ECM fibers compared to axially orientated fibers in both organs. Bilinear fits and a two-fiber family constitutive model showed that the cervix was significantly less distensible than the uterus. We submit that the regional biaxial information reported in this study aids in establishing an appropriate reference configuration for mathematical models of the uterine-cervical complex. Thus, may aid future work to elucidate the biomechanical mechanisms leading to cervical or uterine conditions.     

Mechanical responses of the rat uterus, cervix, and bladder to stimulation of hypogastric and pelvic nerves in vivo

Mechanical activities of the uterus, cervix, and bladder were recorded in vivo in anesthetized rats during electrical stimulation of either the hypogastric or pelvic nerve. Ovariectomized controls and hormone-treated groups were used as well as pregnant and postpartum rats. Stimulation of either hypogastric or pelvic nerve produced voltage- and frequency-dependent contractions of the three organs with no evidence of apparent inhibition. All evoked responses were completely abolished by tetrodotoxin, suggesting that these nerves are common pathways of innervation to the three organs. Atropine abolished uterine and cervical responses to both hypogastric and pelvic nerve stimulation, whereas bladder responses were only partly reduced. Hexamethonium almost totally blocked the evoked responses of the uterus and cervix. Phentolamine partly blocked uterine and cervical responses, and propranolol or physostigmine enhanced uterine and cervical responses to both hypogastric and pelvic nerve stimulation. These results suggest that motor innervation to the rat uterus and cervix is predominantly postganglionic cholinergic, with some alpha- and beta-adrenergic components, and that the bladder is innervated by mainly cholinergic and also noncholinergic nerves. Estrogen and estrogen-plus-progesterone pretreatment significantly increased the responses of uterus and cervix but not bladder. Uterine and cervical responses to either hypogastric or pelvic nerve stimulation were markedly reduced late in pregnancy and reappeared within 7 days after delivery.     

The role of sensory neurons in cervical ripening: effects of estrogen and neuropeptides.

Central nervous system nuclei and circuits, such as the medial preoptic, ventromedial and paraventricular nuclei of the hypothalamus, play important roles in reproduction and parturition, and are influenced by estrogen. Peripheral autonomic and sensory neurons also play important roles in pregnancy and parturition. Moreover, the steroid hormone estrogen acts directly, not only on the reproductive tract organs (uterus and cervix), but also on the central and peripheral nerves by regulating expression of various neuronal genes. The peripheral primary afferent neurons innervating the uterine cervix relay mechanical and biochemical sensory information induced by local cervical events and by passage of fetuses, to the spinal cord and supraspinal centers. Consequently, the birth process in mammals is influenced by the combined action of neurons and hormones. Peripheral sensory stimuli, induced physiologically by fetal expulsion or mechanically by vaginocervical stimulation, alter behavior, as well as autonomic and neuroendocrine systems. Recent evidence indicates that primary afferent neurons innervating the cervix, in addition to their sensory effects, likely exert local "efferent" actions on the ripening cervix near term. These efferent effects may involve estrogen-regulated production of such neuropeptides as substance P and calcitonin gene-related peptide in lumbosacral dorsal root ganglia, and their release in the cervix. Collectively, these findings suggest an interrelationship among estrogen, cervix-related sensory neurons, and local cervical events near term.     

Collagen concentration and biomechanical properties of samples from the lower uterine cervix in relation to age and parity in non-pregnant women

Background  

During normal pregnancy the cervix has a load bearing function. The cervical tissue consists mainly of an extracellular matrix (ECM) rich in collagen; important for the biomechanical properties. The aim of the present study was to evaluate how the biomechanical strength of samples from the distal cervix is associated with collagen content in relation to age and parity. This study demonstrates a method to investigate cervical tissue from women who still have their uterus in situ.     

胎儿纤维连接蛋白与自发性早产预测的研究进展

早产是围生儿死亡和患病的重要原因之一,有效的风险评估可以降低潜在的早产发生风险。胎儿纤维连接蛋白(fetal fibronectin,f FN)是一种细胞外基质的糖蛋白,在胎盘植入、胎盘子宫的细胞黏附、正常妊娠的维持等方面均起重要作用。研究表明,多种产科情况都可导致f FN的异常,临床上通过对孕妇的宫颈阴道分泌物、血浆、羊水中的f FN进行检测,能够预测分娩时间、评估引产的困难程度和胎膜早破发生早产的风险。目前,f FN的测定主要是采取ELISA快速测定方法。本文主要对f FN与早产预测的研究进展进行了综述,其中对f FN的来源以及f FN测试单独或联合宫颈超声预测自发性早产的临床价值作了重点阐述。     

Immunohistochemical demonstration of RECK protein and interleukin-6 in fetal membranes from singleton pregnancies with late preterm delivery,intact membranes and histological chorioamnionitis

ABSTRACT

We investigated whether chorioamnionitis affects immunohistochemical demonstration of RECK protein and interleukin-6 (IL-6) expression in fetal placental membranes following late preterm delivery with intact membranes. Fetal membranes of 28 women with single pregnancy, preterm delivery and histologically documented chorioamnionitis at gestational age 34?36^6/7 weeks constituted the chorioamnionitis study group. The control group consisted of 28 fetal membranes from women with preterm deliveries at the same gestational age without histological chorioamnionitis. Immunohistochemistry was performed using monoclonal antibodies against RECK protein and IL-6. We found a statistically significant difference in RECK expression between the chorioamnionitis and control groups; however, we found no difference in IL-6 expression between the groups. We demonstrated that RECK expression is down-regulated in fetal membranes from pregnancies with spontaneous late preterm birth and intact membranes, which suggests its role in preterm parturition. Equal expression of IL-6 in fetal membranes of pregnancies with and without histological chorioamnionitis is an intriguing and unexpected observation that requires further investigation.     

In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography,Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model

Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE). This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days) by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4–8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000). Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000). Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of its metabolite PGEM. Histological analyses and two-photon excitation microscopy, combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence microscopy (2PF) contrasts, were used to investigate, at the microscopic scale, the structure of cervical tissue. Results show that both collagen and 2PF-active fibrillar structures could be closely related to the mechanical properties of cervical tissue that are perceptible in elastography. In conclusion, SWE may be a valuable method to objectively quantify the cervical stiffness and as a complementary diagnostic tool for preterm birth and for labour induction success.     

The theory of fibre-reinforced composite materials applied to changes in the mechanical properties of the cervix during pregnancy

A theory is presented that relates changes in the mechanical properties of the uterine cervix during pregnancy and the puerperium to changes in biochemical composition. The cervical connective tissue is considered as a fibre-reinforced composite material in which collagen fibres are embedded in a gel-like ground substance. Theories derived from synthetic fibrous composites show that changes in the collagen concentration and organization, alteration of the relative proportions of molecular species in the ground substance and changes in the water content can account for the marked alteration in mechanical properties observed by the end of pregnancy.     

Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage

Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of preterm birth.     

Parturition and recruitment of macrophages in cervix of mice lacking the prostaglandin F receptor

Parturition does not occur in transgenic mice lacking the prostaglandin F receptor (Ptgfr(-/-)) because luteolysis is forestalled and progesterone production persists. Ovariectomy of pregnant Ptgfr(-/-) mice leads to a decline in circulating progesterone and delivery of live pups. The objective of the present study was to test the hypothesis that immigration of macrophages and increased innervation of the cervix of Ptgfr(-/-) mice was associated with ripening and parturition. The cervix of pregnant Ptgfr(-/-) mice was studied on Days 15-21 after breeding; additional groups were ovariectomized on Day 19 of pregnancy, and the cervix obtained on Day 20 of pregnancy before birth or the next day at about 24 h after birth. On Days 18-19 of pregnancy, macrophage numbers and nerve fiber density increased more than 3-fold compared with findings in nonpregnant or Day 15 or 21 pregnant Ptgfr(-/-) mice. The magnitude and time course of these changes were comparable to those found in wild-type controls that delivered on Day 19 after breeding. Thus, the mechanism regulating macrophage immigration, innervation, and cervical remodeling in Ptgfr(-/-) mice with delayed parturition is similar to wild-type controls that deliver at term. By contrast, ovariectomy forestalled the decrease in cervical macrophages in Ptgfr(-/-) mice. By Day 21 after breeding, macrophage numbers more than double those after ovariectomy, relative to those found in pregnant Ptgfr(-/-) mice, whereas nerve fiber density was the same regardless of birth. Density of collagen structure in these mice directly matched macrophage traffic in the cervix. The findings indicate that the prostaglandin F(2alpha) receptor and progesterone withdrawal are a necessary part of the final common pathway for ripening of the cervix and the process of parturition.     

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis

BackgroundPreterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.Methods and findingsWe conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.ConclusionsThese results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.Trial registrationISRCTN Registry ISRCTN 02235181.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02235181","term_id":"NCT02235181"}}NCT02235181.

Jane Norman and co-workers report an evaluation of a cervical pessary for prevention of preterm birth in women with a short cervix bearing twins.     

Evaluation of preterm births and birth defects in liveborn infants of US military women who received smallpox vaccine

BACKGROUND: Women serving in the US military have some unique occupational exposures, including exposure to vaccinations that are rarely required in civilian professions. When vaccinations are inadvertently given during pregnancy, such exposures raise special concerns. These analyses address health outcomes, particularly preterm births and birth defects, among infants who appear to have been exposed to maternal smallpox vaccination in pregnancy. METHODS: This retrospective cohort study included 31,420 infants born to active‐duty military women during 2003–2004. We used Department of Defense databases to define maternal vaccination and infant health outcomes. Multivariable regression models were developed to describe associations between maternal smallpox vaccination and preterm births and birth defects in liveborn infants. RESULTS: There were 7,735 infants identified as born to women ever vaccinated against smallpox, and 672 infants born to women vaccinated in the first trimester of pregnancy. In multivariable modeling, maternal smallpox vaccination in pregnancy was not associated with preterm or extreme preterm delivery. Maternal smallpox vaccination in the first trimester of pregnancy was not significantly associated with overall birth defects (OR 1.40; 95% CI: 0.94, 2.07), or any of seven specific defects individually modeled. CONCLUSIONS: Results may be reassuring that smallpox vaccine, when inadvertently administered to pregnant women, is not associated with preterm delivery or birth defects in liveborn infants. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.     

Loss of Progesterone Receptor-Mediated Actions Induce Preterm Cellular and Structural Remodeling of the Cervix and Premature Birth

A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.