Prevention Of Spontaneous Preterm Birth Research Articles

Prediction and prevention of preterm birth: Quality assessment and systematic review of clinical practice guidelines using the AGREE II framework.

Prediction of pregnancies at risk of preterm birth (PTB) may allow targeted prevention strategies. To assess quality of clinical practice guidelines (CPGs) and identify areas of agreement and contention in prediction and prevention of spontaneous PTB. We searched for CPGs regarding PTB prediction and prevention in asymptomatic singleton pregnancies without language restriction in January 2024. CPGs included were published between July 2017 and December 2023 and contained statements intended to direct clinical practice. CPG quality was assessed using the AGREE-II tool. Recommendations were extracted and grouped under domains of prediction and prevention, in general populations and high-risk groups. We included 37 CPGs from 20 organizations; all were of moderate or high quality overall. There was consensus in prediction of PTB by identification of risk factors and cervical length screening in high-risk pregnancies and prevention of PTB by universal screening and treatment for asymptomatic bacteriuria, screening and treatment for BV in high-risk pregnancies, and use of preventative progesterone and cerclage. Areas of contention or limited consensus were the role of PTB clinics, universal cervical length measurement, biomarkers and cervical pessaries. This review identified strengths and limitations of current PTB CPGs, and areas for future research.

Efficacy and Safety of Low-Dose Aspirin and Vaginal Progesterone in the Prevention of Spontaneous Preterm Birth

Efficacy and Safety of Low-Dose Aspirin and Vaginal Progesterone in the Prevention of Spontaneous Preterm Birth

Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort

Objective: We aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth (sPTB) in singleton pregnancies Methods: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016-June 2020. Exclusion criteria were: lack of documentation regarding whether progestogen was or was not prescribed, delivery outcome unavailable, and pregnancy termination (spontaneous or induced) prior to 16 weeks’ gestation. Exposure of interest was progestogen use with cerclage placement, which included those who were continued on progestogen or who started progestogen after cerclage. Comparator was those without progestogen use after cerclage placement, which included those who had no progestogen use the whole pregnancy, or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. Primary outcome was sPTB <37 weeks. Secondary outcomes were sPTB <34 weeks, gestational age at delivery, composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, Grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, bronchopulmonary dysplasia. There was planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate (17-OHPC)), preterm birth history, and site.Continuous variables compared in adjusted analyses with ANCOVA and categorical variables compared with multivariable logistic regression adjusting for potential confounders with adjusted odds ratio (aOR). Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. Results: During the study period, a total of 699 singletons met inclusion, N=561 in the progestogen with cerclage group, and N=138 with cerclage alone. Baseline characteristics were similar, except those in the progestogen group were more likely to have had a prior sPTB (61% vs 41%, p<0.001). Within the progestogen group, 52% were on 17-OHPC weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of sPTB<37 (31% vs 39% aOR 0.59 (0.39 - 0.89), p=0.01) and <34 weeks (19% vs 27%, aOR 0.55 (0.35 - 0.87), p=0.01), increased latency to spontaneous delivery (Hazard ratio to sPTB <37wk, 0.66 (0.49-0.90), p=0.009), and lower frequency of perinatal death (7% vs 16%, aOR 0.37 (0.20-0.67), p=0.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a prior preterm birth, those with ultrasound or exam-indicated cerclage, those that started progestogen therapy prior to cerclage, and in sites restricted to the United States. Conclusion: Use of progestogen with cerclage was associated with reduced rates of sPTB and early sPTB compared to cerclage alone. Although not powered for subgroups, the strength of evidence for benefit appeared greatest for those with ultrasound or exam-indicated cerclage, and with vaginal progesterone.

Low-Dose Aspirin Use in Pregnancy and the Risk of Preterm Birth: A Swedish Register-Based Cohort Study

ABSTRACT Evidence has shown that low-dose aspirin can reduce the risk of preeclampsia in women with risk factors; more recent evidence has shown that aspirin may also be useful for the prevention of spontaneous preterm birth, even among women without risk factors for preeclampsia. However, there are fewer studies examining the effectiveness of low-dose aspirin in this population, and the studies that have been done have generally been statistically underpowered. This study was meant to address this limitation in a large population of women who had previously experienced preterm birth, assessing whether low-dose aspirin treatment was associated with a lower risk for preterm birth. This study was a register-based cohort study performed using several different Swedish registries. The sample included all women with a first and second singleton birth between 2006 and 2019 and with a preterm birth in the first pregnancy. The primary outcome assessed was preterm birth during the second pregnancy, and secondary outcomes included assessment of preterm birth by severity (moderate preterm was between 32 and 36 weeks' gestation, and severe preterm was less than 32 weeks' gestation) and onset (spontaneous or medically indicated). The variable of interest was low-dose aspirin exposure or at least 1 dispensed prescription of 75 to 160 mg aspirin. The analysis included 22,127 women with a preterm birth in their first pregnancy followed by a second recorded pregnancy. Of this sample, 3057 (14%) were prescribed low-dose aspirin during their second pregnancy. Recurrent preterm birth occurred in 3703 individuals, of whom 547 (15%) had used low-dose aspirin. After adjusting for confounding variables, the incidence of preterm birth was lower in those using low-dose aspirin, with a marginal relative risk (mRR) of 0.87 (95% confidence interval [CI], 0.77–0.99). However, there was no difference in risk for moderate or severe preterm birth (moderate group: mRR, 0.90 [95% CI, 0.78–1.03]; severe group: mRR, 0.75 [95% CI, 0.54–1.04]). In adjusted analyses, there were no statistically significant differences for either medically indicated or spontaneous preterm birth between individuals who used low-dose aspirin and those who did not. The study was limited by its retrospective nature. In addition, the authors acknowledge that a dispensed prescription for aspirin does not necessarily equate to consistent intake of low-dose aspirin throughout a pregnancy. In addition, the population for this study was limited to those who had already experienced a preterm birth, which could affect the generalizability of the results. Although limited differences were found, a small protective effect could not be ruled out, and randomized controlled trials to understand more fully the effect low-dose aspirin might have on preterm birth would be helpful. Further research should also focus on whether the benefits of aspirin use during pregnancy outweigh the potential risks, as well as what the lowest effective dose might be.

How to screen the cervix and reduce the risk of spontaneous preterm birth in asymptomatic women without a prior preterm birth.

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality globally. PTB rates have increased in South Korea despite reduction in birth rates. A history of PTB is a strong predictor of subsequent PTB and screening of cervical length between 16 0/7 weeks and 24 0/7 weeks of gestation is recommended in women with a singleton pregnancy and a prior spontaneous PTB. However, the prediction and prevention of spontaneous PTBs in women without a prior PTB remain a matter of debate. The scope of this review article comprises cervical screening and prevention strategies for PTB in asymptomatic women without a prior PTB, based on recent evidence and guidelines.

Association of Maternal Plasma Manganese with the Risk of Spontaneous Preterm Birth: A Nested Case–Control Study Based on the Beijing Birth Cohort Study (BBCS) in China

We performed this study to clarify the dynamic changes in maternal manganese (Mn) concentration during pregnancy and its association with spontaneous preterm birth (SPB). A nested case-control study was conducted based on the Beijing Birth Cohort Study (BBCS) from 2018 to 2020. Singleton pregnancy women aged 18-44 (n = 488) were involved in the study, including 244 cases of SPB and 244 controls. All of the participants provided blood samples twice (in their first and third trimesters). Inductively coupled plasma mass spectrometry (ICP-MS) was used for the laboratory analysis, and unconditional logistic regression was used for the statistical analysis. We found that the maternal Mn levels were significantly higher in the third trimester than those in the first trimester (median: 1.23 vs. 0.81 ng/mL). The SPB risk was increased to 1.65 (95% CI: 1.04-2.62, p = 0.035) in the highest Mn level (third tertile) in the third trimester, especially in normal-weight women (OR: 2.07, 95% CI: 1.18-3.61, p = 0.011) or non-premature rupture of membrane (PROM) women (OR: 3.93, 95% CI: 2.00-7.74, p < 0.001). Moreover, a dose-dependent relationship exists between the SPB risk and maternal Mn concentration in non-PROM women (P trend < 0.001). In conclusion, dynamic monitoring of maternal Mn level during pregnancy would be helpful for SPB prevention, especially in normal-weight and non-PROM women.

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.

Should case management be considered a component of obstetrical interventions for pregnancies at risk of preterm birth?

Preterm birth remains the leading cause of morbidity and mortality among nonanomalous neonates in the United States. Unfortunately, preterm birth rates remain high despite current medical interventions such as progestogen supplementation and cerclage placement. Case management, which encompasses coordinated care aimed at providing a more comprehensive and supportive environment, is a key component in improving health and reducing costs in other areas of medicine. However, it has not made its way into the general lexicon and practice of obstetrical care. Case management intended for decreasing prematurity or ameliorating its consequences may include specialty clinics, social services, coordination of specialty services such as nutrition counseling, home visits or frequent phone calls by specially trained personnel, and other elements described herein. It is not currently included in nor is it advocated for as a recommended prematurity prevention approach in the American College of Obstetricians and Gynecologists or Society for Maternal-Fetal Medicine guidelines for medically indicated or spontaneous preterm birth prevention. Our review of existing evidence finds consistent reductions or trends toward reductions in preterm birth with case management, particularly among individuals with high a priori risk of preterm birth across systematic reviews, metaanalyses, and randomized controlled studies. These findings suggest that case management has substantial potential to improve the environmental, behavioral, social, and psychological factors with patients at risk of preterm birth.

Comparing the Efficacy of Pessary as an Adjunctive Therapy after Cerclage, and Cerclage Alone in Prevention of Spontaneous Preterm Birth: A Randomized Controlled Trial

Comparing the Efficacy of Pessary as an Adjunctive Therapy after Cerclage, and Cerclage Alone in Prevention of Spontaneous Preterm Birth: A Randomized Controlled Trial

Interventions for the prevention of spontaneous preterm birth: a scoping review of systematic reviews.

BackgroundGlobally, 11% of babies are born preterm each year. Preterm birth (PTB) is a leading cause of neonatal death and under-five mortality and morbidity, with lifelong sequelae in those who survive. PTB disproportionately impacts low/middle-income countries (LMICs) where the burden is highest.ObjectivesThis scoping review sought to the evidence for interventions that reduce the risk of PTB, focusing on the evidence from LMICs and describing how context is considered in evidence synthesis.DesignWe conducted a scoping review, to describe this wide topic area. We searched five electronic databases (2009–2020) and contacted experts to identify relevant systematic reviews of interventions to reduce the risk of PTB. We included published systematic reviews that examined the effectiveness of interventions and their effect on reducing the risk of PTB. Data were extracted and is described narratively.Results139 published systematic reviews were included in the review. Interventions were categorised as primary or secondary. The interventions where the results showed a greater effect size and consistency across review findings included treatment of syphilis and vaginal candidiasis, vitamin D supplementation and cervical cerclage. Included in the 139 reviews were 1372 unique primary source studies. 28% primary studies were undertaken in LMIC contexts and only 4.5% undertaken in a low-income country (LIC) Only 10.8% of the reviews sought to explore the impact of context on findings, and 19.4% reviews did not report the settings or the primary studies.ConclusionThis scoping review highlights the lack of research evidence derived from contexts where the burden of PTB globally is greatest. The lack of rigour in addressing contextual applicability within systematic review methods is also highlighted. This presents a risk of inappropriate and unsafe recommendations for practice within these contexts. It also highlights a need for primary research, developing and testing interventions in LIC settings.

Elevated midtrimester maternal plasma cytokines and preterm birth in patients with cerclage

Cerclage is used for the prevention of spontaneous preterm birth; however, many patients at high risk of spontaneous preterm birth who have a cerclage in place eventually deliver before term. Although inflammation, measured by biomarkers (eg, cytokines), is a known risk factor for preterm delivery, evaluation of inflammation to determine pregnancy outcomes among patients with cerclage is poorly understood. We sought to examine levels of maternal plasma inflammatory cytokines in the midtrimester among asymptomatic patients with a cervical cerclage (placed for any indication, including history, ultrasound, and examination indications) to evaluate the association between cytokine levels and preterm birth. This was a prospective cohort study of singleton, nonanomalous pregnancies who had a cerclage placed at <24 weeks of gestation from 2015 to 2018 at a single tertiary institution. Maternal plasma was collected perioperatively whenever possible. A custom magnetic bead Luminex cytokine assay was used to measure plasma inflammatory cytokine levels from these stored samples. The primary outcome was preterm birth at <37 weeks of gestation. A statistical cut point was calculated for each cytokine level to assess its optimal sensitivity and specificity for spontaneous preterm birth prediction. Patients were classified as having a "high" or "low" result for each cytokine based on this cut point. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and positive and negative predictive values for spontaneous preterm birth prediction. Cox proportional-hazards regression modeled the association between the number of "high" inflammatory cytokines and gestational age at delivery, adjusting for confounders. Additional analyses were performed on the subgroup of patients with history-indicated cerclage and those with an ultrasound- or examination-indicated cerclage. A total of 43 patients participated in this study: 20 (46.5%) had spontaneous preterm birth (median, 30.9 weeks of gestation; interquartile range, 28.4-35.0). Plasma samples were collected at a median of 0 (interquartile range, -2 to 17) days concerning cerclage placement and a median of 18 (interquartile range, 13-21) weeks of gestation. Based on the statistical cut point for each cytokine level, 7% of patients had zero, 20.9% had 1, 18.6% had 2, 20.9% had 3, and 32.6% had ≥4 "high" cytokine results. Each additional "high" cytokine level was associated with earlier delivery (hazard ratio, 1.51; 95% confidence interval, 1.25-1.81) even after controlling for ultrasound- or examination-indication for cerclage (hazard ratio, 1.73; 95% confidence interval, 0.95-3.15). The presence of ≥4 "high" cytokine levels was 70% sensitive and 74% specific for predicting spontaneous preterm birth (area under the curve, 0.846; 95% confidence interval, 0.728-0.964; positive predictive value, 70%; negative predictive value, 73.9%). Among patients with a cervical cerclage, elevated midtrimester maternal plasma cytokine profiles were associated with subsequent preterm birth and can estimate the probability of preterm birth. Confirmation and refinement of this noninvasive panel may provide insight into improved selection of individuals who may benefit from cerclage placement and investigation of therapeutic strategies to mitigate midpregnancy inflammation.

Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234.

Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234.

Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin Summary, Number 234.

Preterm birth is among the most complex and important challenges in obstetrics. Despite decades of research and clinical advancement, approximately 1 in 10 newborns in the United States is born prematurely. These newborns account for approximately three-quarters of perinatal mortality and more than one half of long-term neonatal morbidity, at significant social and economic cost (1-3). Because preterm birth is the common endpoint for multiple pathophysiologic processes, detailed classification schemes for preterm birth phenotype and etiology have been proposed (4, 5). In general, approximately one half of preterm births follow spontaneous preterm labor, about a quarter follow preterm prelabor rupture of membranes (PPROM), and the remaining quarter of preterm births are intentional, medically indicated by maternal or fetal complications. There are pronounced racial disparities in the preterm birth rate in the United States. The purpose of this document is to describe the risk factors, screening methods, and treatments for preventing spontaneous preterm birth, and to review the evidence supporting their roles in clinical practice. This Practice Bulletin has been updated to include information on increasing rates of preterm birth in the United States, disparities in preterm birth rates, and approaches to screening and prevention strategies for patients at risk for spontaneous preterm birth.

Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234.

Preterm birth is among the most complex and important challenges in obstetrics. Despite decades of research and clinical advancement, approximately 1 in 10 newborns in the United States is born prematurely. These newborns account for approximately three-quarters of perinatal mortality and more than one half of long-term neonatal morbidity, at significant social and economic cost (1-3). Because preterm birth is the common endpoint for multiple pathophysiologic processes, detailed classification schemes for preterm birth phenotype and etiology have been proposed (4, 5). In general, approximately one half of preterm births follow spontaneous preterm labor, about a quarter follow preterm prelabor rupture of membranes (PPROM), and the remaining quarter of preterm births are intentional, medically indicated by maternal or fetal complications. There are pronounced racial disparities in the preterm birth rate in the United States. The purpose of this document is to describe the risk factors, screening methods, and treatments for preventing spontaneous preterm birth, and to review the evidence supporting their roles in clinical practice. This Practice Bulletin has been updated to include information on increasing rates of preterm birth in the United States, disparities in preterm birth rates, and approaches to screening and prevention strategies for patients at risk for spontaneous preterm birth.

Controversies in the prevention of spontaneous preterm birth in asymptomatic women: an evidence summary and expert opinion.

Preterm birth prevention is multifaceted and produces many nuanced questions. This review addresses six important clinical questions about preterm birth prevention as voted for by members of the UK Preterm Clinical Network. The questions cover the following areas: preterm birth prevention in 'low-risk' populations; screening for asymptomatic genital tract infection in women at high risk of preterm birth; cervical length screening with cerclage or vaginal pessary insitu; cervical shortening whilst using progesterone; use of vaginal progesterone in combination with cervical cerclage; and optimal advice about intercourse for women at high risk of preterm birth.

The impact of funneling shape on the secondary prevention of spontaneous preterm birth in patients treated with either an Arabin pessary, McDonald cerclage or early total cervical occlusion (ETCO)

Objective Cervical funneling is associated with spontaneous preterm birth (sPTB). The aim of this analysis was to assess the relationship between funneling shape and the response to the McDonald cerclage, the Arabin pessary and the early total cervical occlusion (ETCO). Methods We retrospectively analyzed data of 312 randomly selected singleton pregnancies with cervical shortening <25 mm or normal cervical length and evaluated them according to the progression of funneling: control group (n = 46), cervical shortening without funneling (n = 107), V-shaped funneling (n = 68), U-shaped funneling (n = 47), and prolapse of the amniotic sac (n = 44). We evaluated sPTB rates <34, <28, <32, and <37 weeks as well as prolongation of gestation and birthweight. Results Regarding the rate of sPTB <34 weeks there was no statistical significance in either of the comparisons between control group and each of the four risk groups. Regarding prolongation of gestation we demonstrated a statistical significance for all risk groups compared to the control group (all p < .05) with the lowest prolongation rate noted in the group with amnion prolapse and the highest in the group with isolated cervical shortening without funneling. Similarly, progression of funnel shape resulted in an absolute decrease of birthweight for all risk groups compared to the control group, albeit not significant for the group with U-shaped funneling (p = .1058). Conclusion Independent of the treatment, there was a significant impact of funneling shape on pregnancy duration and birthweight.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial

In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy. The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24+0 and 33+6 weeks. The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24+0 and 33+6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth. We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24+0 and 33+6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31+6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69). In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm.

Guideline No. 398: Progesterone for Prevention of Spontaneous Preterm Birth.

To assess the benefits and risks of progesterone therapy for women at increased risk of spontaneous preterm birth (SPB) and to make recommendations for the use of progesterone to reduce the risk of SPB and improve postnatal outcomes. To administer or withhold progesterone therapy for women deemed to be at high risk of SPB. Preterm birth, neonatal morbidity and mortality, and postnatal outcomes including neurodevelopmental outcomes. Maternity care providers, including midwives, family physicians, and obstetricians. Pregnant women at increased risk of SPB. Medline, PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2018 for medical subject heading (MeSH) terms and keywords related to pregnancy, preterm birth, previous preterm birth, short cervix, uterine anomalies, cervical conization, neonatal morbidity and mortality, and postnatal outcomes. This document represents an abstraction of the evidence rather than a methodological review. This guideline was reviewed by the Maternal-Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the SOGC Board of Directors. Therapy with progesterone significantly reduces the risk of SPB in a subpopulation of women at increased risk. Although this therapy entails a cost to the woman in addition to the discomfort associated with its use, no other adverse effects to the mother or the baby have been identified. RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

In vitro selenium supplementation suppresses key mediators involved in myometrial activation and rupture of fetal membranes.

Spontaneous preterm birth, which can affect up to 20% of all pregnancies, is the greatest contributor to perinatal morbidity and mortality. Infection is the leading pathological cause of spontaneous preterm birth. Infection activates the maternal immune system, resulting in the upregulation of pro-inflammatory and pro-labor mediators that activate myometrial contractions and rupture of fetal membranes. Anti-inflammatory agents therefore have the potential for the prevention of spontaneous preterm birth. Selenium, an essential micronutrient, has been shown to be a potent anti-inflammatory regulator. Notably, clinical and epidemiological studies have suggested a link between selenium and preterm birth. Thus, the aim of this study was to assess the effect of selenite (an inorganic form of selenium) on the expression of pro-inflammatory and pro-labor mediators in human gestational tissues. Human fetal membranes and myometrium were pre-incubated with or without selenite before incubation with the bacterial product lipopolysaccharide (LPS) to stimulate inflammation associated with preterm birth. Selenite blocked LPS-induced expression of pro-inflammatory cytokines and chemokines and enzymes involved in remodelling of myometrium and degradation of fetal membranes. Of note, selenite also suppressed myometrial activation induced by inflammation as evidenced by a decrease in LPS-induced prostaglandin signalling and myometrial cell contractility. These effects of selenite were mediated by the MAPK protein ERK as selenite blunted LPS induced activation of ERK. In conclusion, selenite suppresses key mediators involved in inflammation induced activation of mediators involved in active labor in human fetal membranes and myometrium. These findings support recent clinical studies demonstrating selenium supplementation is associated with decreased incidence of spontaneous preterm birth.