Correction: Acceptability of a trial of vaginal progesterone for the prevention of preterm birth among HIV-infected women in Lusaka, Zambia: A mixed methods study.
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SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC7842881 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Correction: Acceptability of a trial of vaginal progesterone for the prevention of preterm birth among HIV-infected women in Lusaka, Zambia: A mixed methods study.
PloS one 20210128 1
[This corrects the article DOI: 10.1371/journal.pone.0238748.]. ...[more]
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Project description:Antenatal progesterone prevents preterm birth (PTB) in women with a short cervix or prior PTB in daily vaginal or weekly injectable formulations, respectively. Neither has been tested for the indication of maternal HIV, which is associated with an elevated risk of PTB. The Vaginal Progesterone (VP) Trial was a pilot feasibility study of VP to prevent HIV-related PTB in Lusaka, Zambia. Using mixed methods, we concurrently evaluated the acceptability of the trial and the study product among participants. Over a 1-year period, we enrolled 140 pregnant women living with HIV into a double-masked, placebo-controlled, randomized trial of daily self-administered VP or placebo. We administered an endline questionnaire to all participants and conducted in-depth interviews with 30 participants to assess barriers and facilitators to uptake and retention in the trial and to study product adherence. All interviews were audiotaped, transcribed, translated into English as needed, and independently coded by two analysts to capture emerging themes. Of 131 participants who completed the questionnaire, 128 (98%) reported that nothing was difficult when asked the hardest part about using the study product. When given a hypothetical choice between vaginal and injectable progesterone, 97 (74%) chose vaginal, 31 (24%) injectable, and 3 (2%) stated no preference. Most interviewees reported no difficulties with using the study product; others cited minor side effects and surmountable challenges. Strategies that supported adherence included setting alarms, aligning dosing with antiretrovirals, receiving encouragement from friends and family, sensing a benefit to their unborn baby, and positive feedback from study staff. Participants who reported preference of a vaginal medication over injectable described familiarity with the vaginal product, a fear of needles and resulting pain, and inconvenience of a weekly clinic visit. Those who would prefer weekly injections cited fewer doses to remember. Perceived barriers to study participation included mistrust about the motivations behind research, suspicion of Satanism, and futility or possible harm from a placebo. We report key influences on acceptability of a randomized trial of VP to prevent PTB among HIV-infected women in Zambia, which should inform methods to promote uptake, adherence, and retention in a full-scale trial.
| S-EPMC7514015 | biostudies-literature
Project description:BackgroundWomen infected with HIV have a risk of preterm birth (PTB) that is twice that among uninfected women, and treatment with antiretroviral therapy (ART) may further increase this risk. Progesterone supplementation reduces the risk of preterm delivery in women who have a shortened cervix in the midtrimester. We propose to study the feasibility of a trial of vaginal progesterone (VP) to prevent PTB among HIV-infected women receiving ART in pregnancy. Given low adherence among women self-administering vaginal study product in recent microbicide trials, we plan to investigate whether adequate adherence to VP can be achieved prior to launching a full-scale efficacy trial.Methods and designOne hundred forty HIV-infected pregnant women in Lusaka, Zambia, will be randomly allocated to daily self-administration of either VP or matched placebo, starting between 20 and 24 gestational weeks. The primary outcome will be adherence, defined as the proportion of participants who achieve at least 80% use of study product, assessed objectively with a validated dye stain assay that confirms vaginal insertion of returned single-use applicators. Secondary outcomes will be study uptake, retention, and preliminary efficacy. We will concurrently perform semi-structured interviews with participants enrolled in the study and with women who decline enrollment to assess the acceptability of VP to prevent PTB and of enrollment to a randomized controlled trial.DiscussionWe hypothesize that VP could prevent PTB among women receiving ART in pregnancy. In preparation for a trial to test this hypothesis, we plan to assess whether participants will be adherent to study product and protocol.Trial registrationClinicalTrial.gov, NCT02970552.
| S-EPMC5516378 | biostudies-literature
Project description:ObjectiveTo determine the effect of intramuscular progesterone on the vaginal immune response of pregnant women with a history of prior preterm birth.MethodsA prospective, cohort study of women at 11-16 weeks gestation, ?18 years of age, and carrying a singleton pregnancy was conducted from June 2016 to August 2017 after IRB approval. Women in the progesterone arm had a history of preterm birth and received weekly intramuscular 17-hydroxyprogesterone caproate. Controls comprised of women with healthy, uncomplicated pregnancies. Excluded were women with vaginitis, diabetes mellitus, hypertension, or other chronic diseases affecting the immune response. A vaginal wash was performed at enrollment, at 26-28 weeks, and at 35-36 weeks gestation. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and a P value <0.05 was considered significant.ResultsThere were 39 women included, 10 with a prior preterm birth and 29 controls. The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, BMI, gestational age at delivery, mode of delivery, and birth weight. Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2±25.1% versus 26.1±13.2%; P = 0.04), IL-1 beta (47.9±26.4% versus 24.9±17%; P<0.01), IL-2 (16.7±9.3% versus 11.3±6.3%; P = 0.03), and IL-13 (16.9±12.4% versus 8.2±7.4%; P = 0.01) were significantly elevated compared to controls. In the third trimester the cytokine densities for IL-1 alpha (26.0±18.2% versus 22.3±12.0%; P = 0.49), IL-1 beta (31.8±15.9% versus 33.1±16.8%; P = 0.84), IL-2 (10.0±8.4% versus 10.9±5.9%; P = 0.71), and IL-13 (9.1±5.9% versus 10.0±6.5%; P = 0.71) were all statistically similar between the progesterone arm and controls, respectively.ConclusionThere is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following the administration of 17- hydroxyprogesterone caproate to levels similar to healthy controls.
| S-EPMC6312274 | biostudies-literature
Project description:Antenatal vaginal progesterone (VP) reduces the risk of preterm birth (PTB) in women with shortened cervical length, and we hypothesize that it may also prevent PTB in women with HIV as their primary risk factor. We conducted a pilot feasibility study in Lusaka, Zambia to investigate uptake, adherence, and retention in preparation for a future efficacy trial. This was a double-masked, placebo-controlled, randomized trial of 200mg daily self-administered VP suppository or placebo. Pregnant women with HIV who were initiating or continuing antiretroviral therapy were eligible for participation. Potential participants underwent ultrasound to assess eligibility; we excluded those ≥24 gestational weeks, with non-viable, multiple gestation, or extrauterine pregnancies, with short cervix (<2.0cm), or with prior spontaneous PTB. Participants initiated study product between 20-24 weeks of gestation and continued to 37 weeks (or delivery, if sooner). The primary outcome was adherence (proportion achieving ≥80% study product use), assessed by dye stain assay of returned single-use vaginal applicators. Secondary outcomes with pre-defined feasibility targets were: uptake (≥50% eligible participants enrolled) and retention (≥90% ascertainment of delivery outcomes). We also evaluated preliminary efficacy by comparing the risk of spontaneous PTB <37 weeks between groups. From July 2017 to June 2018, 208 HIV-infected pregnant women were eligible for screening and 140 (uptake = 67%) were randomly allocated to VP (n = 70) or placebo (n = 70). Mean adherence was 94% (SD±9.4); 91% (n = 125/137) achieved overall adherence ≥80%. Delivery outcomes were ascertained from 134 (96%) participants. Spontaneous PTB occurred in 10 participants (15%) receiving placebo and 8 (12%) receiving progesterone (RR 0.82; 95%CI:0.34-1.97). Spontaneous PTB < 34 weeks occurred in 6 (9%) receiving placebo and 4 (6%) receiving progesterone (RR 0.67; 95%CI:0.20-2.67). In contrast to findings from vaginal microbicide studies in HIV-uninfected, non-pregnant women, our trial participants were highly adherent to daily self-administered vaginal progesterone. The study's a priori criteria for uptake, adherence, and retention were met, indicating that a phase III efficacy trial would be feasible.
| S-EPMC6988922 | biostudies-literature
Project description:BackgroundProgesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child.MethodsWe did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373.FindingsBetween Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61-1·22) or neonatal outcome (OR 0·62, 0·38-1·03), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in means -0·48, 95% CI -2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27).InterpretationVaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age.FundingEfficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales.
| S-EPMC5406617 | biostudies-literature
Project description:The prevention and treatment of preterm birth remains one of the biggest challenges in obstetrics. Worldwide, 11% of all children are born prematurely with far-reaching consequences for the children concerned, their families and the health system. Experimental studies suggest that progesterone inhibits uterine contractions, stabilises the cervix and has immunomodulatory effects. Recent years have seen the publication of numerous clinical trials using progestogens for the prevention of preterm birth. As a result of different inclusion criteria and the use of different progestogens and their methods of administration, it is difficult to draw comparisons between these studies. A critical evaluation of the available studies was therefore carried out on the basis of a search of the literature (1956 to 09/2018). Taking into account the most recent randomised, controlled studies, the following evidence-based recommendations emerge: In asymptomatic women with singleton pregnancies and a short cervical length on ultrasound of ??25?mm before 24 weeks of gestation (WG), daily administration of vaginal progesterone (200?mg capsule or 90?mg gel) up until 36?+?6 WG leads to a significant reduction in the preterm birth rate and an improvement in neonatal outcome. The latest data also suggest positive effects of treatment with progesterone in cases of twin pregnancies with a short cervical length on ultrasound of ??25?mm before 24 WG. The study data for the administration of progesterone in women with singleton pregnancies with a previous preterm birth have become much more heterogeneous, however. It is not possible to make a general recommendation for this indication at present, and decisions must therefore be made on a case-by-case basis. Even if progesterone use is considered to be safe in terms of possible long-term consequences, exposure should be avoided where it is not indicated. Careful patient selection is crucial for the success of treatment.
| S-EPMC6690740 | biostudies-literature
Project description: Not available
| S-EPMC3893814 | biostudies-literature
Project description:BackgroundThe aim of this study is to evaluate the efficacy of vaginal progesterone to prevent preterm delivery in twin pregnancies and its effect on perinatal outcome.Materials and methodsA randomized, open label, controlled trial (NCT02350231) was carried out over 70 women, in three different hospitals in Egypt, between February 2015 and January 2017. All eligible pregnant women with twin pregnancies were randomly allocated in a 1:1 ratio into two groups. Group I (Progesterone group) was dispensed, 400 mg of progesterone through a vaginal pessary, each day at bedtime, from the 28th week of pregnancy until delivery. Group II (Control group) received no treatment other than the normal tonics taken during pregnancy. The two study groups were followed until delivery. The primary outcome was the rate of preterm delivery <37 weeks.ResultsNo significant differences were observed among both groups of women in terms of delivery <37 weeks (16.9% versus 25.4%; p=0.06) and mode of delivery (vaginal versus cesarean; p=0.31). The mean gestational age at delivery was comparable between both groups (p=0.09). Additionally, no difference, regarding the neonatal outcome, was observed between both groups.ConclusionDispensing vaginal progesterone [400 mg] after 28 weeks of gestation does not prevent preterm delivery in twin gestations.
| S-EPMC6516185 | biostudies-literature
Project description:The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.
| S-EPMC6750801 | biostudies-literature
Project description:The interaction between the vaginal microbiome, cervical length and vaginal progesterone treatment for preterm birth risk
| PRJEB12577 | ENA