Prevention Of Preterm Birth Research Articles

Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution

The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth.

Progesterone and Treatment for Preterm Birth: Past, Present and Future

Abstract: Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality in the United States and worldwide. Efforts to predict and delay preterm birth have been largely unsuccessful thus far. This paper seeks to illuminate the history and relevant discoveries regarding the role of progesterone in the prevention of PTB, which includes maintaining quiescence of the myometrium and counteracting cervical ripening. We will review the outcomes and methodologies of recent clinical trials, which have led to debate over the efficacy of progesterone in delaying PTB among at-risk women. The aim of this paper is to explore the historical and scientific basis for progestin treatments in the prevention of PTB, briefly discuss the results of recent clinical trials, and suggest direction for future research.

Preconception laparoscopic cervical cerclage for prevention of mid-trimester pregnancy loss and preterm birth: A 6-year study

ObjectiveTo evaluate surgical results and pregnancy outcomes of preconception laparoscopic cervical cerclage (LCC) in women with cervical insufficiency. Study designWe conducted an observational study in consecutive women who had preconception LCC. Data was prospectively collected from 55 women at high risk of second trimester miscarriage and extreme preterm delivery due to cervical insufficiency who underwent pre-conception LCC between January 2017 – December 2021. This included patient demographics and relevant obstetric & gynaecological history, previous cervical cerclage, operative complications and subsequent pregnancy outcomes. All women included in study had at least one previous unsuccessful transvaginal cervical cerclage. The surgeries were conducted in private tertiary hospital in Hyderabad, India. The follow-up was until December 2022. The primary outcome was neonatal survival. Surgical morbidity and complications were also recorded. ResultsThere were 49 pregnancies of which 46 progressed beyond first trimester. 4.34 % (2/46) were delivered between 28 and 33 weeks due to preterm premature rupture of membranes (PPROM). 13.04 % (6/46) including 5 women with pregnancy complications and one with unicornuate uterus needed delivery between 34 and 36 weeks. 82.60 % (38/46) women were delivered at or beyond 37 weeks of pregnancy. In those who carried pregnancy beyond first trimester, live-birth rate and neonatal survival rate were 100 %. All neonates had favourable outcome with no long-term morbidity. There were no intraoperative or immediate postoperative complications. Two women had long-term complication in the form of tape erosion needing further surgery. ConclusionsThis study provides evidence that LCC improves pregnancy outcomes significantly in those with cervical weakness, without increasing the safety risk.

Primary prevention with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth: results of the Preterm Labor Prevention Using Vaginal Antiseptics study

Preterm labor is one of the leading causes of perinatal death and is currently considered a syndrome with many causes. One of the most important causes of preterm birth is ascending infection from bacterial vaginosis. Chlorhexidine has proven to be effective against bacterial vaginosis and against bacterial biofilms without affecting gestation. We aimed to evaluate the effectiveness of a universal primary prevention strategy for preterm birth using intravaginal chlorhexidine applied before 16 weeks (Preterm Labor Prevention Using Vaginal Antiseptics study). We performed a prospective observational study with 2 cohorts of pregnant women that were assigned either to prevention of preterm birth by means of intravaginal chlorhexidine (Cum Laude Chlorhexidine, chlorhexidine digluconate 0.2%) before 16 weeks (n=413), or to no treatment following the usual hospital protocol (n=704). Primary outcomes were the incidence of spontaneous preterm birth before 34 and 37 weeks; the incidence of preterm birth before 34 and 37 weeks, including inductions for premature rupture of membranes; and the incidence of preterm birth before 34 and 37 weeks, including any indication for termination of pregnancy. Both cohorts were compared using Mann-Whitney and Fisher tests. Finally, a multivariable analysis, including the odds ratio was performed, adjusting for clinical parameters, to evaluate the importance of the different determinants in the prediction of preterm birth. In pregnancies treated with chlorhexidine, the incidences of spontaneous preterm birth; preterm birth, including induction for premature rupture of membranas; and preterm birth, including any indication for termination of pregnancy were at 34 and 37 weeks: 0% and 0%, 0.24% and 1.69, and 2.90% and 3.15%, respectively; whereas in nontreated pregnancies, these incidences were 9% and 11%, 12% and 23%, and 35% and 43%, respectively. According to the multivariable analysis, the incidence of preterm birth among women treated with chlorhexidine before 16 weeks was halved (Odds ratio, 0.52; P<.05). Universal treatment with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth, especially before 34 weeks.

Randomized controlled trials: not always the “gold standard” for evidence in obstetrics and gynecology

Randomized Controlled Trials (RCTs) are considered the "gold standard" for therapeutic interventions, and it is not uncommon for sweeping changes in medical practice to follow positive results from such trials. However, RCTs are not without their limitations. Physicians frequently view RCTs as infallible, while they tend to dismiss evidence derived from sources other than RCTs as less credible or reliable. In several situations in obstetrics & gynecology, there are no RCTs to help guide the clinician. In these circumstances, it is important to evaluate the entire body of evidence including observational studies, rather than to dismiss interventions altogether simply because no RCTs exist. RCTs and observational studies should be viewed as complementary to each other rather than at odds with each other. Some reversals in widely adopted clinical practice have recently been implemented following subsequent studies that contradicted the outcomes of major RCTs; the most notable of these being the withdrawal from the market of 17-hydroxyprogesterone caproate for preterm birth prevention. Such reversals could potentially have been averted if the inherent limitations of RCTs were carefully considered prior to implementing these universal practice changes. This Clinical Opinion underscores the limitations of an exclusive reliance on RCTs while disregarding other evidence in determining how best to care for patients. Solutions are proposed that advocate that clinicians adopt a more balanced perspective that considers the entirety of the available medical evidence as well as the individual patient characteristics, needs, and wishes.

FRI406 Maternal Biomarkers Of Adiposity And Stress For Preterm Birth

Abstract Disclosure: G. Mayne: None. P.E. DeWitt: None. J. Wen: None. U. Christians: None. D. Dabelea: None. J. Schulkin: None. K. Hurt: None. Background: Adiponectin is a potent uterine tocolytic and decreases with gestational age, so it could be a maternal metabolic quiescence factor during pregnancy. Maternal stress can influence risk for preterm birth, and adiponectin may be inversely related to cortisol. Therefore, we characterized a potential mechanistic link between preterm birth, adiponectin, and cortisol. In this pilot study, we hypothesized maternal plasma adiponectin and cortisol concentrations are inversely related and that lower adiponectin and higher cortisol associate with spontaneous preterm birth. Methods: We performed a nested case-control study using biobank morning fasting plasma samples, taken twice in pregnancy for the Healthy Start pre-birth cohort. We included low-risk women with singleton pregnancies and excluded mothers with major medical illness, preeclampsia, chronic hypertension, or prior preterm birth. We matched preterm cases with term controls (1:3) by gestational age at first blood sample and least variation in time between blood samples (16 preterm, 46 term). We quantified high (HMW), low molecular weight (LMW), and total adiponectin using an ELISA assay. We also quantified cortisol and five related steroid hormones from the same specimens using HPLC/mass spectrometry. We used generalized estimating equations and additive models to compare group means and associations between adiponectin and cortisol. We used machine learning with gradient boosting for predictive modeling. Results: Contrary to our hypothesis, total, HMW, and LMW adiponectin positively associated with cortisol across gestation (P&amp;lt;0.001 for all), however the association was reduced in the preterm compared with term group and significantly so for LMW (P=0.044). In predictive modelling, HMW adiponectin, maternal pre-pregnancy BMI, maternal age, and cortisol were the four most highly relevant predictors for preterm birth (AUROC=0.704). Conclusion: In healthy low-risk patients, we found associations between adiponectin and cortisol differ across gestation for pregnancies ending with term or preterm delivery and have some predictive value in this cohort. This suggests a possible mechanistic link between maternal metabolism and stress for pregnancy maintenance. These biomarkers may prove useful as predictors in larger studies and might indicate possible maternal metabolic therapies for preterm birth prevention. Presentation: Friday, June 16, 2023

Using the Delphi Technique to Achieve Consensus on Prevention and Treatment of Preterm Single Birth in China

Abstract Objective This study aimed to reach a consensus among obstetric experts on the prevention and treatment of preterm single births in China. Methods Based on the scoping literature review and the 2014 edition of preterm birth of Clinical Diagnosis and Treatment guidelines, we generated the Delphi survey statements with five evaluation dimensions, including the definition of preterm birth, exclusion of risk factors for preterm birth, prevention, and prediction of preterm birth, treatment of preterm birth, and evaluation of intervention outcomes of preterm birth. Obstetric experts from the Obstetrics and Gynecology Branch of the Chinese Medical Association formed the expert group for this survey. All the obstetric experts participated two-round modified Delphi survey via an anonymous online survey and an online panel. Mean scores, rank sum, full score ratio, and the lowest score ratio were calculated to reflect the concentration of expert opinions. The coefficient of variation and Kendall W coefficient were used to reflect the expert opinion coordination degree of the survey statement. Results The expert response rate for both rounds of surveys was 100% (41/41). Experts reached an agreement on 36 statements in five dimensions of preterm birth prevention and treatment in the first round of the survey and reached a consensus on the remaining 13 statements in the second round. A total of 49 statements (mean scores ≥3, full score ratio ≥20%, coefficient of variation ≤0.3) were explicitly included in this guideline to form recommendations, while the remaining three clinical issues that did not reach a consensus require further determination based on evidence quality. The Kendall W coefficient in the two rounds of the Delphi survey were 0.20 (P &lt; 0.001) and 0.29 (P &lt; 0.001). Conclusion The five dimensions and 49 statements, agreed upon through a two-round Delphi study, determined the recommended statements to be included in the updated guidelines for the prevention and treatment of preterm birth in China. The defined lower limit is set at ≥28 gestational weeks; however, an update has been made to the definition of premature birth, specifying that “with the consent of the mother and her family, treatment is not abandoned for viable infants ≥26 gestational weeks.”

OP11.05: Cervical cerclage for prevention of preterm birth in twin pregnancies: systematic review and meta‐analysis

OP11.05: Cervical cerclage for prevention of preterm birth in twin pregnancies: systematic review and meta‐analysis

EP19.21: Transabdominal cervical length screening in mid‐pregnancy for preterm birth prevention: the impact of image quality on cervical length measurement

EP19.21: Transabdominal cervical length screening in mid‐pregnancy for preterm birth prevention: the impact of image quality on cervical length measurement

Screening and Prevention of Preterm Birth in Twin Pregnancies.

Twins represent 3.2% of all live births. However, they account for 20% of all preterm deliveries, 60% delivering <37 weeks, 10.7% <32 weeks, and 5 times higher risk of infant death. Risk factors for preterm birth (PTB) include the history of preterm delivery, monochorionic twins, short cervical length, and cervical surgery. Transvaginal cervical length <24 weeks is the best tool to predict PTB. Only vaginal progesterone in women with transvaginal cervical length <25mm and physical exam indicated cerclage in women with cervical dilation >1cm have shown a significant decrease in PTB and improvement in neonatal outcomes.

Role Of Low Dose Aspirin In Preventing Preterm Birth In Patients With Previous History Of Preterm Delivery

Objective: Preterm birth (PTB) occurs between 24-37 weeks of gestation. The important risk factor for PTB is a previous PTB and currently progesterone is used for the management of recurrent spontaneous PTB. Some studies have shown good outcomes but recent studies revealed that the use of vaginal progesterone was not related to a decreased likelihood of PTB or neonatal adverse effects. Thus, the controversy in the literature suggests multiple underlying pathological mechanisms involved in the progression of PTB. This study aims to determine the role of low-dose aspirin in the prevention of preterm birth in patients with a previous history of preterm delivery. Methodology: In this randomized controlled trial, a total of 172 patients fulfilling the inclusion criteria were selected from the inpatient and outpatient departments. Patients were divided randomly into two groups (group A and group B), using random number tables. In Group A, low-dose aspirin (75mg) was given while group B was taken as a control group. Patients were called every 8 weeks in the outpatient department for the assessment of compliance and side effects of the drug. The data were entered and analyzed by using SPSS v25.0. Chi-square was used to compare the two groups for incidence of preterm birth. Relative risk (along with a 95% confidence interval) for the decrease in the incidence of preterm birth with the use of aspirin was calculated. Results: The age of participants included in the study was 18 to 40 years. The mean age of patients in group A was 33.85±5.210 years and in group B was 32.86±4.139 years. The mean fetal birth weight in group A was 2281.1962±363.125 grams and in group B was 2271.4344±374.797 grams. In the low-dose aspirin group, 10(11.6%) had preterm birth and 31(36.0%) in the control group with a p-value of 0.001, which is statistically significant. The risk of having preterm birth with low-dose aspirin was 1.801 times less than controls. Conclusion: aspirin in low dose given before 14 weeks of gestation decrease spontaneous preterm birth as compared to the control group in a woman with a history of previous preterm birth which was spontaneous

First-trimester prediction of preterm pre-eclampsia and prophylaxis by aspirin: Effect on spontaneous and iatrogenic preterm birth.

To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB. Secondary analysis of data from the SPREE study and the ASPRE trial. Multicentre studies. In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE). Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.

The Need for Biomedical Engineering Research and Innovation in Preterm Birth Prevention and Management

The Need for Biomedical Engineering Research and Innovation in Preterm Birth Prevention and Management

A cross-sectional survey of women’s views and preferences for preterm birth screening and treatment

ObjectivesPrimary outcomes were to determine; 1) the desire for more patient information from healthcare professionals on preterm birth (PTB) prevention 2) the desire for PTB screening surveillance or participation in research or 3) the acceptability of transvaginal ultrasound (TVUS) or vaginal examinations to predict spontaneous PTB. MethodsA 19-question, piloted, self-administered survey was completed by unselected pregnant women in a tertiary maternity hospital in Dublin, Ireland. Data was collected to include maternal socio-demographics, past obstetric history, and current pregnancy details, in addition to views and preferences on PTB screening and preventative treatments. Statistical analysis to include binary and multinomial regression was performed by IBM SPSS Statistics for Windows (Version 29.0). Results277 women completed the study survey. 9.4% of women had attended the preterm birth surveillance clinic (PSC). 75.1% of respondents indicated a preference for more information from healthcare professionals about PTB. 65% reported that TVUS and vaginal examinations were acceptable in pregnancy. The acceptability of antenatal examinations was significantly influenced by ethnicity; white European (OR 2.58, CI 1.12–5.95, p = 0.003) and Asian (OR 3.39, CI 1.18–9.67, p = 0.02). Discomfort (25.3%) and vaginal bleeding (11.9%) were the most frequently reported concerns about TVUS. 95.7% of unselected women indicated that they would accept treatment to prevent PTB. Vaginal progesterone (53.8%) was preferred treatment compared to cervical cerclage (15.9%) or cervical pessary (16.6%).55.6% of respondents stated they attend or wish to attend for additional appointments or research opportunities for PTB screening. Women with a previous PTB or second trimester miscarriage were more likely to attend or wish to attend for PTB screening (OR 3.23, CI 1.34–7.79, p = 0.009). ConclusionPTB is an important healthcare priority for pregnant women in Ireland. However, women require more information, counselling and reassurance about the utility and safety of TVUS in PSCs.

COVID-19 lockdown related to decrease in premature birth rate and increase in birth weight in metropolitan France.

The worldwide rate of preterm birth (PTB) has been increasing over the last two decades. COVID-19 lockdowns provide a unique opportunity to assess the effects of socioenvironmental and lifestyle factors on premature birth and birth weight. We explored the effects of COVID-19 lockdowns on the PTB rate and birth weight at a nationwide scale in France until one year after their occurrence. This national retrospective observational study evaluated the rate of PTB and birth weight in France from January 2016 to December 2020. Data were obtained from the national Programme Médicalisé des Systèmes d'Information database. The rates of global and sub-categories of PTB were tested. The birth weight was studied before and after lockdown for all live births, for term and premature neonates, and for each category of low birth weight (LBW) by a stratified analysis. Data from 2,949,372 births from January 2016 to December 2019, including 228,857 PTB, were compared to those of 699,344 births and 51,886 PTB from January to December 2020. The national rate of PTB decreased significantly from 7.7% to 7.3%, when compared with the 2016-2019 period. This decrease was persistent up to 9 months later. It was observed only for moderate PTB, whereas very PTB and extremely PTB remained stable. The national mean birth weight for full-term babies increased after the lockdown and was still observable up to 8 months later (+0.16%, p < 0.0001). The proportion of children with LBW also decreased 2 months after lockdown (-0.15%; p = 0.02). For VLBW, the difference only appeared over the 6-month post-lockdown period (-0.06%; p = 0.006). This nationwide study shows a significant reduction in prematurity and a significant increase in birth weight in France after the lockdown for a period of time not limited to the lockdown itself. A more in-depth study of the factors determining these variations may help to drive PTB prevention policies.

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.

Research prioritisation on prevention and management of preterm birth in low and middle-income countries (LMICs) with a special focus on Bangladesh using the Child Health and Nutrition Research Initiative (CHNRI) method.

Fifteen million babies are born preterm globally each year, with 81% occurring in low- and middle-income countries (LMICs). Preterm birth complications are the leading cause of newborn deaths and significantly impact health, quality of life, and costs of health services. Improving outcomes for newborns and their families requires prioritising research for developing practical, scalable solutions, especially in low-resource settings such as Bangladesh. We aimed to identify research priorities related to preventing and managing preterm birth in LMICs for 2021-2030, with a special focus on Bangladesh. We adopted the Child Health and Nutrition Research Initiative (CHNRI) method to set research priorities for preventing and managing preterm birth. Seventy-six experts submitted 490 research questions online, which we collated into 95 unique questions and sent for scoring to all experts. A hundred and nine experts scored the questions using five pre-selected criteria: answerability, effectiveness, deliverability, maximum potential for burden reduction, and effect on equity. We calculated weighted and unweighted research priority scores and average expert agreement to generate a list of top-ranked research questions for LMICs and Bangladesh. Health systems and policy research dominated the top 20 identified priorities for LMICs, such as understanding and improving uptake of the facility and community-based Kangaroo Mother Care (KMC), promoting breastfeeding, improving referral and transport networks, evaluating the impact of the use of skilled attendants, quality improvement activities, and exploring barriers to antenatal steroid use. Several of the top 20 questions also focused on screening high-risk women or the general population of women, understanding the causes of preterm birth, or managing preterm babies with illnesses (jaundice, sepsis and retinopathy of prematurity). There was a high overlap between research priorities in LMICs and Bangladesh. This exercise, aimed at identifying priorities for preterm birth prevention and management research in LMICs, especially in Bangladesh, found research on improving the care of preterm babies to be more important in reducing the burden of preterm birth and accelerating the attainment of Sustainable Development Goal 3 target of newborn deaths, by 2030.

Leveraging the host immune:microbe interaction for preterm birth prediction and prevention

Leveraging the host immune:microbe interaction for preterm birth prediction and prevention

W4 - Midwives at the centre of preterm birth prevention

W4 - Midwives at the centre of preterm birth prevention

Few randomized trials in preterm birth prevention meet predefined usefulness criteria

ObjectivesWe operationalized a research usefulness tool identified through literature searches and consensus and examined if randomized controlled trials (RCTs) addressing preterm birth prevention met predefined criteria for usefulness. Study Design and SettingThe usefulness tool included eight criteria combining 13 items. RCTs were evaluated for compliance with each item by multiple assessors (reviewer agreement 95–98%). Proportions of compliances with 95% confidence interval (CI) were calculated and change over time was assessed using ≧ 2010 as a cutoff. ResultsAmong 347 selected RCTs, published within 56 preterm birth Cochrane reviews, only 36 (10%, 95% CI = 7–14%) met more than half of the usefulness criteria. Compared to trials before 2010, recent trials used composite or surrogate (less informative) outcomes more often (13% vs. 25%, relative risk 1.91, 95% CI = 1.21–3.00). Only 16 trials reflected real practice (pragmatism) in design (5%, 95% CI = 3–7%), with no improvements over time. No trials reported involvement of mothers to reflect patients’ research priorities and outcomes selection. Recent trials were more transparent. ConclusionFew preterm birth prevention RCTs met more than half of the usefulness criteria but most of usefulness criteria are improving after 2010. Use of informative outcomes, patient centeredness, pragmatism and transparency should be key targets for future research planning.