Preterm Birth In High-risk Women Research Articles

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

Cervical cerclage training: Development and assessment of a simulator

Cervical cerclage is a mainstay intervention for the prevention of spontaneous preterm birth in high-risk women. Simulation training facilitates high-level skill transfer in a low-consequence environment, and is being integrated into obstetrics and gynecology training. This study aimed to develop a simulator for cervical cerclage, determine its validity as a simulator, and identify parameters suitable as proxy markers for performance. The 3 aims of this study were achieved, namely: (1) simulator design by obstetricians and a commercial company; (2) survey of obstetricians and gynecologists across a variety of training stages to determine need for and opinion of the simulator; and (3) comparison of novice and expert groups across a variety of proxy markers for successful cerclage insertion. Obstetricians and gynecologists found the simulator to be similar to clinical scenarios and suitable for skill training. Novice participants stated that the use of the simulator improved their confidence (P=.016). In a comparison between 6 expert and 8 novice surgeons, there seemed to be variations across multiple measurements of cerclage placement. Simulation is an increasingly prominent training modality for surgical skills. The simulator described herein was considered suitable for training by obstetricians and gynecologists. Further work should focus on the validations of proxy markers of successful insertion, longitudinal assessment of trainees, and correlation of training outcomes with clinical outcomes.

Interventions to prevent spontaneous preterm birth in high-risk women with singleton pregnancy: a systematic review and network meta-analysis

© 2019 The Cochrane Collaboration. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the efficacy of current, relevant interventions to prevent preterm birth in women with singleton pregnancy and high individual risk of spontaneous preterm birth. We will consider interventions for women with a history of spontaneous preterm birth or short cervical length and women with asymptomatic vaginal infections.

Prediction of preterm labour from a single blood test: The role of the endocannabinoid system in predicting preterm birth in high-risk women

ObjectiveTo determine if plasma concentrations of the N-acylethanolamines (NAEs) N-arachidonoylethanolamine (AEA), N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA) increase in women at high risk for preterm birth (PTB) and whether these could be used to predict preterm delivery and if so, how they compare with current methods. DesignProspective cohort study. SettingA large UK teaching hospital. Population217 pregnant women were recruited between 24 and 34 gestational weeks at ‘high-risk’ for PTB, recruited from a prematurity prevention clinic or antenatal wards. MethodsPlasma AEA, OEA, and PEA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry whilst FAAH enzyme activity was measured by fluorometric radiometric assay and CL by ultrasound scan. The clinical usefulness of these measurements were determined by ROC and multivariate analyses. ResultsAEA and PEA concentrations were significantly higher in women who delivered prematurely. An AEA concentration >1.095 nM predicted PTB, the gestational age at delivery and the recruitment to delivery interval (RTDI). A PEA concentration >17.50 nM only predicted PTB; FAAH enzyme activity was not related to these changes. Multivariate analysis (all variables) generated an equation to accurately predict the RTDI. ConclusionsA single plasma AEA or PEA measurement can predict PTB. A single AEA measurement predicts the gestational age of delivery and the remaining period of pregnancy with reasonable accuracy and better than existing conventional tests thus offering a better window for primary prevention of PTB.

Predictive value of cervical cytokine, antimicrobial and microflora levels for pre-term birth in high-risk women

Spontaneous preterm birth (sPTB, delivery <37 weeks gestation), accounts for approximately 10% of births worldwide; the aetiology is multifactorial with intra-amniotic infection being one contributing factor. This study aimed to determine whether asymptomatic women with a history of sPTB or cervical surgery have altered levels of inflammatory/antimicrobial mediators and/or microflora within cervical fluid at 22–24 weeks gestation. External cervical fluid was collected from women with history of previous sPTB and/or cervical surgery at 22–24 weeks gestation (n = 135). Cytokine and antimicrobial peptides were measured on a multiplex platform or by ELISA. qPCR was performed for detection of 7 potentially pathogenic bacterial species. IL-8 and IL-1β levels were lower in women who delivered preterm compared to those who delivered at term (IL-8 P = 0.02; IL-1β P = 0.04). There were no differences in elafin or human beta defensin-1 protein levels between the two groups. Multiple bacterial species were detected in a higher proportion of women who delivered preterm than in those who delivered at term (P = 0.005). Cervical fluid IL-8 and IL-1β and microflora have the potential to be used as biomarkers to predict sPTB in high risk women.

Gender and preterm birth: Is male fetal gender a clinically important risk factor for preterm birth in high-risk women?

Gender differences in several adverse pregnancy outcomes have been described, including preterm labour and delivery. In the low risk population, the male fetus is at significantly higher risk of spontaneous preterm birth. ObjectivesOur objective was to examine the risk effect of fetal gender on pregnant women at higher risk of preterm birth, and therefore its potential impact on targeting management. Study designThis was an analysis of prospectively collected data from a dedicated inner-city Prematurity Surveillance Clinic over a sixteen-year period. All women were high-risk for preterm delivery in view of their history, which included previous late miscarriage, PTB or significant cervical surgery. Obstetric variables and pregnancy outcomes were compared in male and female babies. Demographic and risk factors were compared between groups, and both spontaneous and iatrogenic preterm delivery rates interrogated (<24, <28, <34 and <37 weeks’ gestation). Risk ratios (with 95% confidence intervals) were calculated for each gestational band. ResultsIn this cohort, 14.5% of women (363/2505) delivered before 37 weeks. Pregnant women were stratified by fetal gender and were comparable for referral risk factors and demographic characteristics. There was no significant association between fetal gender and incidence of miscarriage less than 24 weeks (RR 1.17, 95% CI 0.65–2.10, p = 0.607), or preterm births 24 to 37 weeks RR 1.07 (95% CI 0.82–1.40, p = 0.383). Furthermore, analysis by gestational band [<28 RR 0.91 (95% CI 0.60–1.37, p = 0.647), <34 RR 1.18 (95% CI 0.89–1.57, p = 0.257 and <37 weeks RR 1.10 (95% CI 0.91–1.33, p = 0.309)] also showed no effect. This held true for both spontaneous and iatrogenic preterm delivery. In our high-risk cohort there was no gender difference for preeclampsia (RR 0.93, 95% CI 0.61 to 1.41, p = 0.725) or preterm premature rupture of membranes (PPROM) (RR 1.14, 95% CI 0.86 to 1.50, p = 0.384) ConclusionsIn a high-risk cohort there was no significant increased risk of miscarriage, spontaneous or iatrogenic PTB, preeclampsia or PPROM for the male fetus. This is contradictory to low-risk populations and confirms that gender need not be integrated into high-risk management protocols for preterm birth.

Can the optimal cervical length for placing ultrasound-indicated cerclage be identified?

To assess a continuum of cervical length (CL) cut-offs for the efficacy of ultrasound-indicated cerclage in women with previous spontaneous preterm birth (PTB). This was a planned secondary analysis of a multicenter randomized clinical trial of ultrasound-indicated cerclage for the prevention of PTB in high-risk women. The efficacy of cerclage for preventing recurrent PTB < 35, < 32 and < 24 weeks' gestation was assessed using multivariable logistic regression analysis. Odds ratios (ORs) and CIs were estimated for a range of CL cut-offs using bootstrap regression. The 2.5(th) and 97.5(th) percentiles of bootstrapped ORs determined the CIs. Results were illustrated using smoothed curves superimposed on estimated ORs by CL cut-off. Of 301 women with a CL < 25 mm, 142 underwent ultrasound-indicated cerclage and 159 did not have cerclage placement. The few cases with CL < 10 mm limited the evaluation to CL cut-offs between < 10 mm and < 25 mm. For PTB < 35 weeks, ORs in women with a cerclage and CL < 25 mm were statistically significantly lower than in those without cerclage, and efficacy was maintained at smaller CL cut-offs. Results were similar for PTB < 32 weeks. For PTB < 24 weeks, results differed, with ORs increasing toward unity (no benefit), with wide CIs, for CL cut-offs between < 10 mm and < 15 mm, attributed to the small number of births < 24 weeks. The efficacy of ultrasound-indicated cerclage in women with previous spontaneous PTB varies by action point CL cut-off and by PTB gestational age of interest. Cerclage significantly reduces the risk of PTB < 35 and < 32 weeks, at CL cut-offs between < 10 mm and < 25 mm, with the greatest reduction at shorter CL, affirming that women with prior spontaneous PTB and a short CL are appropriate candidates for ultrasound-indicated cerclage. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Progesterone.

Progestogens are a promising treatment in the prevention of spontaneous preterm birth in high-risk women. In women with a prior history of spontaneous preterm delivery and in women with a sonographic shortened cervix, there is considerable evidence supporting a benefit of progestogen therapy in the reduction of preterm delivery. In women with multifetal gestations, progestogen therapy has not been shown to be beneficial. Data are inconclusive in women with arrested preterm labor. Questions remain about the mechanism of progestogen action, the optimal type of progestogen, the best mode of administration, and the ideal dosing regimen.

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P4), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P4 may help reduce the incidence of preterm birth in high-risk women.

The value of maternal serum progesterone and cholesterol levels and cervical transvaginal gray-scale histogram in predicting preterm birth in high-risk women

Background Preterm labor (PTL) is a challenging gynecological problem that is accountable for high rates of perinatal mortality and morbidity. Low maternal serum cholesterol and progesterone levels are associated with preterm birth. Measurement of cervical length, funneling, and consistency are essential in screening for PTL. Objective The aim of the study was to show a correlation between maternal serum progesterone and cholesterol levels and cervical transvaginal gray-scale histogram at 20–25 weeks in the prediction of preterm birth in high-risk women. Patients and methods The study included 100 patients at high risk for PTL attending Minia Maternity University Hospital. Levels of progesterone and cholesterol were analyzed and a cervical transvaginal histogram to determine cervical glandular/stromal ratio was performed for all patients at 20–25 weeks of gestation. Results PTL occurred in 30 of 100 women. Increased incidence of spontaneous PTL was seen in patients with a short cervix and increased funneling. Serum progesterone was significantly (P=0.001) lower in women who delivered preterm (80.6±27.5) compared with women who delivered at term (116.1±15.8). Also, serum cholesterol was significantly (P=0.001) lower in women who delivered preterm (156.6±35.4) than in women who delivered at term (185.6±42.3). Glandular/stromal ratio was significantly lower (P<0.001) in women who delivered preterm (0.31±0.04) than in those who delivered at term (0.98±0.02). Conclusion Glandular/stromal ratio, serum progesterone and cholesterol levels, and transvaginal ultrasound findings can predict PTL in high-risk women. They can also be used for prevention of PTL.

Vaginal Progesterone to Prevent Preterm Birth in High-Risk Women

Preterm birth is a significant problem in the United States, contributing to neonatal morbidity and mortality. Progesterone is a hormone naturally produced by the corpus luteum and the placenta in early pregnancy and is essential for maintaining pregnancy. Clinicians and researchers have used this hormone in later gestation to try to prevent preterm birth. However, mechanisms of action, indications for use, dosing and administration have varied and are not fully understood. This article revisits two recent randomized controlled trials in which researchers investigated the effectiveness of vaginal progesterone suppositories and gel in the prevention of preterm birth among women who were at high risk for delivering prematurely.

The development of an iphone application to predict preterm birth in high risk women

IntroductionFetal fibronectin (fFN) and cervical length are the best predictors of preterm birth (PTB). No studies have attempted to predict PTB in asymptomatic high risk women by combining demographics, past...

Does midtrimester cervical length ≥25 mm predict preterm birth in high-risk women?

We sought to assess pregnancy outcome along a continuum of cervical lengths (CLs) ≥25 mm. We conducted planned secondary analysis of a randomized cerclage trial of women with prior spontaneous preterm birth 17(0)-34(6/7) weeks. Outcomes of women who maintained CLs ≥25 mm were analyzed. Women with CLs <25 mm randomized to no cerclage comprised an internal comparison group. Of 1014 screened, 153 had CL <25 mm, and 672 had CL ≥25 mm. Birth <35 weeks occurred in 16% of the ≥25 mm cohort. The relationship between CLs ≥25 mm and birth gestational age was null (P = .15). In the <25 mm group, progressively shorter CLs predicted birth <35 weeks (P < .001); this relationship was null in the ≥25 mm group (P = .17). The continuum of CLs ≥25 mm measured between 16(0/7)-22(6/7) weeks does not predict gestational length in women with prior spontaneous preterm birth.

What Is the Optimal Gestational Age for History-Indicated Cerclage Placement?

We estimated the optimal gestational age for placement of a history-indicated cerclage in a retrospective cohort study of pregnancies during the period between 1994 to 2007. Pregnancies were divided into two groups: group 1, cerclage <14 weeks (N = 83), and group 2, cerclage >or=14 weeks (N = 59). The primary outcome was spontaneous preterm birth (SPTB) <35 weeks. Parametric and nonparametric tests were performed where appropriate. One hundred forty-two pregnancies by 130 women were included. Demographic characteristics were similar between groups. The median gestational age at cerclage was 12 weeks (group 1) and 15 weeks (group 2). There was no difference in the primary outcome, incidence of SPTB <35 weeks (17% versus 20%; P = 0.59) between groups 1 and 2, respectively. Likewise, the secondary outcomes, mean gestational age at birth (38 versus 37 weeks; P = 0.96), incidence of low birth weight (28% versus 23%; P = 0.50), and the incidence of preterm premature rupture of membranes (17% versus 18%; P = 0.89) were similar between groups. No other gestational age cutoff was predictive of SPTB <35 weeks using a receiver operator characteristic curve (13 to 17 weeks; area = 0.52; P = 0.64). Gestational age of history-indicated cerclage placement was not associated with a significant effect on preterm birth in high-risk women. The optimal gestational age for placement of a history-indicated cerclage is probably 12 to 14 weeks, after screening for fetal anomalies and aneuploidy.

Does progesterone (P4) alter expression of toll-like receptor-2 (TLR2) and toll-interacting protein (Tollip) in vaginal and cervical epithelial cells?

Recent clinical studies have suggested that supplemental progesterone, (P4) may be effective at preventing preterm birth in high-risk women but the mechanism of action is unclear. We hypothesized that P4 enhances the ability of epithelial cells in the reproductive tract to detect and respond to pathogens before they can ascend into the upper genital tract. Many pathogens associated with preterm birth are recognized through TLR2 whose signal transduction pathways are negatively regulated by Tollip.

Incidence of preterm birth in high-risk women with a singleton gestation by cervical length and gestational age

Incidence of preterm birth in high-risk women with a singleton gestation by cervical length and gestational age

Can shortened midtrimester cervical length predict very early spontaneous preterm birth?

Objective The study was undertaken to test the hypothesis that shortened midtrimester cervical length is more predictive of early (<26 weeks) than later (26-34 weeks) spontaneous preterm birth. Study design This is a secondary analysis of a blinded, multicenter observational study of 183 women with a prior preterm birth. Vaginal sonography was begun at 16 to18 weeks' gestation and scheduled every 2 weeks (maximum 4 scans per patient). Cervical length and any observed dynamic shortening were recorded at each visit to determine the shortest observed cervical length from 16 to 24 weeks' gestation. The shortest cervical length measurements were categorized as less than 25 mm, 25 to 29 mm and 30 mm or greater. The initial cervical length was also compared with the shortest cervical length to categorize patients on the basis of the timing of cervical shortening 30 mm or less. Contingency table, linear regression, and survival analysis were used to analyze the relationship between cervical length groups and spontaneous preterm birth. Results In both the less than 25 mm and 25 to 29 mm groups, the incidence of spontaneous midtrimester birth (<26 weeks) was higher than the incidence of later (26-34 weeks) preterm birth (<25 mm group: 37% vs 19%; 25-29 mm group: 16% vs 3%, respectively) as compared with women with a shortest cervical length 30 mm or greater, who had rates of 1% and 9% respectively ( P < .0001). Similarly, women who had an initial cervical length 30 mm or less and those who shortened their cervix to 30 mm or less before 22 weeks were also more likely to experience a midtrimester than later preterm birth, whereas women who shortened their cervix 30 mm or less later (22-24 weeks) or who maintained a cervical length greater than 30 mm had lower rates of midtrimester than later preterm birth ( P < .0001). Conclusion Shortened cervical length in the midtrimester preferentially predicts early, as opposed to later, spontaneous preterm birth in high-risk women.