Dataset Information

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

ABSTRACT:

Background

There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.

Methods

Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass.

Results

The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development.

Conclusions

This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.

SUBMITTER: McDougall ARA

PROVIDER: S-EPMC10354994 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

McDougall Annie R A ARA Hastie Roxanne R Goldstein Maya M Tuttle Andrew A Ammerdorffer Anne A Gülmezoglu A Metin AM Vogel Joshua P JP

BMC pregnancy and childbirth 20230718 1

<h4>Background</h4>There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the m ...[more]

PMID: 37464260

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Project description:Preterm birth is one of the major global health problems and part of the Millennium Development goals because of the associated high number of perinatal or neonatal mortality and long-term risks of neurodevelopmental and metabolic diseases. Transvaginal sonography has meanwhile been established as a screening tool for spontaneous preterm birth despite its relatively low sensitivity when considering only the cervical length. Vaginal progesterone has been shown to reduce prematurity rates below 34 weeks in a screening population of singleton pregnancies. Up to now, no positive long-term effect could be demonstrated after 2 years. It seems to have no benefit to prolong pregnancies after a period of preterm contractions and in risk patients without cervical shortening. Meta-analyses still demonstrate conflicting results dependent on quality criteria used for selection. A cerclage is only indicated in singleton pregnancies with previous spontaneous preterm birth and a combined cervical shortening in the current pregnancy. Nevertheless, the short- and long-term outcome has never been evaluated, whereas maternal complications may be increased. There is no evidence for a prophylactic cervical cerclage in twin pregnancies even in cases with cervical shortening. Emergency cerclage remains an indication after individual counseling. The effect of a cervical pessary in singleton pregnancy seems to be more pronounced in studies where a few investigators with increasing experience have treated and followed the patients at risk for preterm birth. Mainly in twin pregnancies, pessary treatment seems to be promising compared to other treatment options of secondary prevention when the therapy is started at early stages of precocious cervical ripening. At present, several international trials with the goal to reduce global rates of prematurity are in progress which will hopefully allow to specify the indications and methods of intervention for certain subgroups. When trials are summarized, prospective meta-analyses carry a lower risk of bias than the meanwhile uncontrolled magnitude of retrospective meta-analyses with conflicting results.

Project description:BackgroundA hypothesis of preterm parturition is that the pathogenesis of spontaneous preterm birth (sPTB) may be associated with an inflammatory process. Based on this theory, we have hypothesized that an inflammatory biomarker, procalcitonin (PCT), may be a good predictive marker of sPTB at the admission for threatened preterm labour (TPL). The present study was aimed to investigate the association between serum PCT and sPTB in women with TPL and to evaluate whether PCT levels may predict sPTB in women with TPL within 7 or 14 days.MethodsIn a prospective observational laboratory-based study, women with singleton pregnancies, TPL between 24 and 36 weeks and intact membranes, were enrolled between January 2014 and June 2016. Participants received routine medical management of TPL (tocolysis with atosiban, antenatal corticosteroids, and biological tests at admission (C-reactive protein, white blood cell count, and PCT measured on electrochemiluminescence immunoassay)). The primary endpoint was sPTB before 37 weeks of gestation. The value of serum PCT levels to predict sPTB within 7 or 14 days were evaluated using receiver-operating curves (ROC) analysis.ResultsA total of 124 women were included in our study. PCT levels did not statistically differ between women with sPTB (n = 30, 24.2%) and controls (n = 94) (median in ng/mL [interquartile range]: 0.043 [0.02-0.07] compared to 0.042 [0.02-0.13], respectively; P = 0.56). PCT levels did not also statistically differ between women with sPTB within 7 days (n = 7, 5.6%) or 14 days (n = 12, 9.7%) after testing and controls. Moreover, subgroup analysis revealed no difference among PCT levels at admission between 24 and 28 weeks, between 28 and 32 weeks and over 32 weeks, and controls. On the basis of the receiver-operating characteristic curve, the highest sensitivity and specificity corresponded to a PCT concentration of 0.038 ng/mL, with poor predictive values for sPTB within 7 or 14 days.ConclusionSerum PCT was not relevant to predict sPTB within 7 or 14 days in women admitted with TPL between 24 and 36 weeks, and thus it is not a suitable biological marker to confirm the hypothesis of an inflammatory process associated with preterm parturition.Trial registrationClinicaltrials.gov ( NCT01977079 ), Registered 24 October 2013.

Project description: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.

Project description:IntroductionThe ability to predict spontaneous preterm birth (sPTB) prior to labour onset is a challenge, and it is currently unclear which biomarker(s), may be potentially predictive of sPTB, and whether their predictive power has any utility. A systematic review was conducted to identify maternal blood biomarkers of sPTB.MethodsThis study was conducted according to PRISMA protocol for systematic reviews. Four databases (MEDLINE, EMBASE, CINAHL, Scopus) were searched up to September 2021 using search terms: "preterm labor", "biomarker" and "blood OR serum OR plasma". Studies assessing blood biomarkers prior to labour onset against the outcome sPTB were eligible for inclusion. Risk of bias was assessed based on the Newcastle Ottawa scale. Increased odds of sPTB associated with maternal blood biomarkers, as reported by odds ratios (OR), or predictive scores were synthesized. This review was not prospectively registered.ResultsSeventy-seven primary research articles met the inclusion criteria, reporting 278 unique markers significantly associated with and/or predictive of sPTB in at least one study. The most frequently investigated biomarkers were those measured during maternal serum screen tests for aneuploidy, or inflammatory cytokines, though no single biomarker was clearly predictive of sPTB based on the synthesized evidence. Immune and signaling pathways were enriched within the set of biomarkers and both at the level of protein and gene expression.ConclusionThere is currently no known predictive biomarker for sPTB. Inflammatory and immune biomarkers show promise, but positive reporting bias limits the utility of results. The biomarkers identified may be more predictive in multi-marker models instead of as single predictors. Omics-style studies provide promising avenues for the identification of novel (and multiple) biomarkers. This will require larger studies with adequate power, with consideration of gestational age and the heterogeneity of sPTB to identify a set of biomarkers predictive of sPTB.

Dataset Information

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

Background

Methods

Results

Conclusions

Publications

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.

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