Management Of Preterm Labor Research Articles

The Association between Parathyroid Hormone and Preterm Labor

Abstract Background Preterm labor represents the main cause of both neonatal mortality and the childhood mortality as it accounts for (35% of 2.8 million neonatal deaths) and (17% of 6.3 million childhood deaths) worldwide. Parathyroid hormone regulates feto-placental mineral homeostasis and stimulates placental calcium transfer. Myometrial activity is directly related to cytoplasmic free calcium, and reduced calcium concentrations inhibit contractions. Aim of the Work We aim to explore the possible association between PTH, calcium, magnesium, phosphorus & albumin levels and preterm labor. Thus, it might be used as a predictor to help prophylaxis, early diagnosis or add another diagnostic tool for preterm labor and further management. Patients and Methods At Ain Shams University Maternity Hospital we conducted a case control on one hundred pregnant women who were recruited from the outpatient clinic and labor ward assessed for eligibility and were enrolled in this study and classified into two groups. Group A: Cases: 50 women who were having established preterm labor and Group B: Controls: 50 matched pregnant women with gestational age (28-36 weeks). Results Mean parathyroid hormone in preterm in labor group was 42.13 while in other preterm not in labor was 50.77 and mean albumin in preterm in labor group 4.02 was while it 4.36 was in the other group so the results shows that there is no statistically-significant difference between the two studied groups regarding the laboratory data except a very small variability between the mean of albumin that can't make any difference to our conclusion. Conclusion We found that there is no obvious association between parathyroid hormone and preterm labor.

Involvement of ObRb receptor, nitric oxide, and BKCa channel signaling pathways in leptin-induced relaxation of pregnant mouse uterus

The purpose of this study was to determine the receptor subtype and the underlying mechanisms involved in the relaxant effect to leptin in mid- and late-pregnant mouse uterus. We determined the relative mRNA expression of receptor subtypes, eNOS, and BKCa channel by quantitative PCR and also the overall receptor expression by immunohistochemistry. Isometric tension studies were conducted to evaluate the effects of leptin and to delineate its mechanisms. A selective siRNA for the ObRb receptor was used to determine the participation of the receptor subtype in biochemical and molecular effects of leptin.The relaxant response to leptin was greater in mid-pregnancy compared to late pregnancy and was mediated by the activation of BKCa channels by eNOS-derived nitric oxide in an ObRb receptor-dependent manner. In comparison to mid-pregnancy, expression of short forms (mainly ObRa receptor) of the receptor was significantly increased in late pregnancy, whereas ObRb receptor expression was similar in both phases.The results of the study suggest that ObRb receptor mediates leptin-induced increase in eNOS expression and NO synthesis. Leptin-induced eNOS expression and activation cause cGMP-independent stimulation of BKCa channels causing uterine relaxation. Increased short forms of the receptors and reduced BKCa channels exert a negative effect on uterine relaxation in late pregnancy. Leptin may have a physiological role in maintaining uterine quiescence in mid-pregnancy and its reduced relaxant response in late gestation may facilitate labor. Further, ObRb receptor agonists may be useful in the management of preterm labor.

Management, Utilization, and Outcomes of Preterm Labor in an Integrated Health Care System.

Fetal fibronectin (fFN) testing and transvaginal ultrasound (TVUS) are diagnostic tools used to predict impending spontaneous preterm birth (sPTB) among women presenting with preterm labor (PTL). We evaluated the association between fFN testing or TVUS cervical length (CL) measurement in predicting sPTB, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, and sPTB-related costs. We conducted a retrospective cohort study using data from the Kaiser Permanente Southern California electronic health system (January 1, 2009-December 31, 2020) using diagnostic and procedure codes, along with a natural language processing algorithm to identify pregnancies with PTL evaluations. PTL evaluation was defined as having fFN and/or TVUS assessment. Outcomes were ascertained using diagnostic, procedural, and diagnosis-related group codes. Multivariable logistic regression assessed the association between fFN and/or TVUS results and perinatal outcomes. Compared with those without PTL evaluations, those with positive fFN tests had higher adjusted odds ratio (adj.OR) for sPTB (2.95, 95% confidence interval [CI]: 2.64, 3.29), RDS (2.34, 95% CI: 2.03, 2.69), and NICU admission (2.24, 95% CI: 2.01, 2.50). In contrast, those who tested negative had lower odds for sPTB (adj.OR: 0.75, 95% CI: 0.70, 0.79), RDS (adj.OR: 0.67, 95% CI: 0.61, 0.73), and NICU admission (adj.OR: 0.74, 95% CI: 0.70, 0.79). Among those with positive fFN results, the odds of sPTB was inversely associated with CL. Health care costs for mothers and neonates were lowest for those with fFN testing only. This study demonstrates that positive fFN results were associated with an increased odds of sPTB, RDS, and NICU admission and the association with sPTB was inversely proportional to CL. Additionally, negative fFN results were associated with decreased odds of sPTB, RDS, and NICU admissions. fFN testing may predict these and other sPTB-related adverse outcomes hence its utility should be explored further. Moreover, fFN testing has some cost savings over TVUS. · Patients with positive fFN tests had higher odds of sPTB, RDS, and NICU admission.. · Inverse relationship between sPTB and CL among those with positive fFN tests was observed.. · Health care costs for mothers and neonates were lowest for those with fFN testing only..

Tocolytic effectiveness of nifedipine in management of preterm labor: A tertiary center experience

Objective: This study aimed to compare the efficacy of nifedipine use in our clinic for treatment of preterm labor with diferent effacement degrees, and to compare our results with the literature. Methods: 440 singleton pregnant women with intact amnionic membrane pregnant women in their 23 and 36 weeks were retrospectively evaluated. Because of different criterias defining preterm labor in the literature, patients were divided into two groups as 4 or over contractions in 20 minutes and cervical opening at 2 cm and/or above and/or effachment at 80% or above (Group A, n=230) and 4 or over contractions in 20 minutes and cervical opening below 2 min and effechment below 80% (Group B, n=210). Descriptive statistics were conducted using chi-square and Mann Whitney U test, and statistically significance was p <0.05. Results: Demographics, reproductive history and pregnancy weeks of the groups were similar. The average time between the start of tocolysis and the birth was 4 times higer in Group B (0.1-99.2, mean 28.4) than that of Group A (0.1-78.9, mean 7.4 days, p<0.001). Delay after tocoloysis at days 1 to 7 was statistically remarkable in Group B (p<0.001, for each). Preterm labor resulting in early birth was more remarkable in Group A in both before 34 weeks and 37 weeks (p<0.001, for each; n=88, 38.3% vs n=36, 17.1% and n=171, 74.3% vs n=98, 46.7%, respectively and n=269/124, 28.2 vs 61.1%). Delay with nifedipine at day 1 (87.5%), day 2 (79.1%), day 3 (74.8%) and day 7 (65.5%) was also compatable with the literature. Conclusions: Nifedipine is an effective tocolytic agent in preterm labor regardless of the effachment degree.

Comparison of the efficacy of nifedipine with ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor: a systematic review and meta-analysis

BackgroundSome studies have compared the efficacy of nifedipine with that of other tocolytic drugs in the treatment of preterm labor, but the reported results are conflicting.ObjectiveTo compare the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor.MethodsIn this systematic review and meta-analysis, PubMed/MEDLINE, Scopus, Clarivate Analytics Web of Science, and Google Scholar were searched until April 3,2024 using predefined keywords. Randomized controlled trials (RCTs) and clinical trials that compared the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor were included. Two authors independently reviewed the articles, assessed their quality and extracted the data. The quality of the included RCTs based on the Cochrane Risk of Bias Tool 1 for clinical trial studies. The risk difference (RD) with the associated 95% confidence interval (CI) was calculated. A forest plot diagram was used to show the comparative point estimates of nifedipine and other tocolytic drugs on the prevention of preterm labor and their associated 95% confidence intervals based on the duration of pregnancy prolongation. Study heterogeneity was evaluated by the I2 index, and publication bias was evaluated by Egger’s test.ResultsForty studies enrolling 4336 women were included. According to our meta-analysis, there was a significant difference in the prolongation of preterm labor within the first 48 h between the nifedipine group and the nitroglycerine group (RD, -0.04; 95% CI, -0.08 to -0.00; I2: 32.3%). Additionally, there were significant differences between nifedipine and ritodrine (RD, 0.11; 95% CI, 0.02 to 0.21; I2, 51.2%) for more than one week RD, 0.10; 95% CI, 0.03 to 0.19; I2, 33.2%) and for 34 weeks and more. The difference between nifedipine and magnesium sulfate was not significant in any of the four time points.ConclusionsConsidering the superiority of nifedipine over ritodrine and nitroglycerine and its similar efficacy to magnesium sulfate for tocolysis, it seems that the side effects of these options determine the first drug line.

A pivotal role for the IL-1β and the inflammasome in preterm labor

During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1β), leading to myometrial contraction. Although IL-1β is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1β was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1β in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1β was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.

Phenanthroline relaxes uterine contractions induced by diverse contractile agents by decreasing cytosolic calcium concentration

Uterine contractions during labor and preterm labor are influenced by a complex interplay of factors, including hormones and inflammatory mediators. This complexity may contribute to the limited efficacy of current tocolytics for preterm labor, a significant challenge in obstetrics with 15 million cases annually and approximately 1 million resulting deaths worldwide. We have previously shown that the myometrium expresses bitter taste receptors (TAS2Rs) and that their activation leads to uterine relaxation. Here, we investigated whether the selective TAS2R5 agonist phenanthroline can induce relaxation across a spectrum of human uterine contractions and whether the underlying mechanism involves changes in intracellular Ca2+ signaling. We performed experiments using samples from pregnant women undergoing scheduled cesarean delivery, assessing responses to various inflammatory mediators and oxytocin with and without phenanthroline. Our results showed that phenanthroline concentration-dependently inhibited contractions induced by PGF2α, U46619, 5-HT, endothelin-1 and oxytocin. Furthermore, in hTERT-infected human myometrial cells exposed to uterotonics, phenanthroline effectively suppressed the increase in intracellular Ca2+ concentration induced by PGF2α, U46619, oxytocin, and endothelin-1. These results suggest that the selective TAS2R5 agonist may not only significantly reduce uterine contractions but also decrease intracellular Ca2+ levels. This study highlights the potential development of TAS2R5 agonists as a new class of uterine relaxants, providing a novel avenue for improving the management of preterm labor.

A Comparative Study Between Intravenous Magnesium Sulphate and Intravenous Isoxsuprine for Arrest of Preterm Labour

Introduction: Wide use of medical management of preterm labour has been obstructed due to low success rate of arrest of labour. This is aggravated by higher incidence of serious side effect of the available tocolytic agents, especially beta-mimetic tocolytics. With this background, the present study was carried out to compare the efficacy and maternal side effect of magnesium sulphate and Isoxsuprine in the arrest of preterm labour
 Methodology: This was a comparative prospective interventional study conducted among pregnant women coming to department of obstetrics and gynaecology with 28 to 37 weeks of gestation. Patients were divided in to two groups - Group 1 receiving Isoxsuprine and Group 2 receiving Magnesium Sulphate. Base line profile and outcome were compared between the two study groups.
 Results: Magnesium sulphate was more effective in arresting labour compared to Isoxsuprine (p<0.05). Tachycardia and hypotension were observed more frequently in group1 (Isoxsuprine) compared to group 2 (MgSO4). In cases having <1 cm dilatation and or less than 25% effacement MgSO4 was significantly more effective that Isoxsuprine for tocolysis.
 Conclusion: Magnesium sulphate is a more effective tocolytic agent than Isoxsuprine. Magnesium sulphate produce lesser maternal and foetal side effects like hypotension, palpitation, tachycardia as compared to Isoxsuprine.

PGF2α induces a pro-labour phenotypical switch in human myometrial cells that can be inhibited with PGF2α receptor antagonists.

Preterm birth is the leading cause of infant morbidity and mortality. There has been an interest in developing prostaglandin F2α (PGF2α) antagonists as a new treatment for preterm birth, although much of the rationale for their use is based on studies in rodents where PGF2α initiates labour by regressing the corpus luteum and reducing systemic progesterone concentrations. How PGF2α antagonism would act in humans who do not have a fall in systemic progesterone remains unclear. One possibility, in addition to an acute stimulation of contractions, is a direct alteration of the myometrial smooth muscle cell state towards a pro-labour phenotype. In this study, we developed an immortalised myometrial cell line, MYLA, derived from myometrial tissue obtained from a pregnant, non-labouring patient, as well as a novel class of PGF2α receptor (FP) antagonist. We verified the functionality of the cell line by stimulation with PGF2α, resulting in Gαq-specific coupling and Ca2+ release, which were inhibited by FP antagonism. Compared to four published FP receptor antagonists, the novel FP antagonist N582707 was the most potent compound [Fmax 7.67 ± 0.63 (IC50 21.26nM), AUC 7.30 ± 0.32 (IC50 50.43nM), and frequency of Ca2+ oscillations 7.66 ± 0.41 (IC50 22.15nM)]. RNA-sequencing of the MYLA cell line at 1, 3, 6, 12, 24, and 48h post PGF2α treatment revealed a transforming phenotype from a fibroblastic to smooth muscle mRNA profile. PGF2α treatment increased the expression of MYLK, CALD1, and CNN1 as well as the pro-labour genes OXTR, IL6, and IL11, which were inhibited by FP antagonism. Concomitant with the inhibition of a smooth muscle, pro-labour transition, FP antagonism increased the expression of the fibroblast marker genes DCN, FBLN1, and PDGFRA. Our findings suggest that in addition to the well-described acute contractile effect, PGF2α transforms myometrial smooth muscle cells from a myofibroblast to a smooth muscle, pro-labour-like state and that the novel compound N582707 has the potential for prophylactic use in preterm labour management beyond its use as an acute tocolytic drug.

Nifedipine versus magnesium sulfate in the management of preterm labour- A randomised controlled trial

Preterm labour is the leading cause of perinatal morbidity and mortality worldwide. Preterm birth accounts for 75% of neonatal deaths and 50% of long-term morbidity including respiratory disease and neuro-developmental impairment. The use of tocolysis in women in preterm labour aims to inhibit uterine contractions and reduce perinatal morbidity and mortality associated with early delivery.To study the effect and compare the efficacy of Nifedipine and Magnesium sulphate in management of preterm labour.: This randomized controlled trial was performed on 80 women with preterm labor between 28 and 37 weeks of gestation who were randomly assigned to receive either MgSO4 or nifedipine. All patients were checked for successful prolongation of pregnancy who had not been delivered at 48 hours [primary tocolytics effects] and more than 7 days [secondary tocolytics effects] after beginning the treatment and side effects of tocolysis.: From 80 patients, 40 received nifedipine and 40 received MgSO4. There were no differences in suppression of labor pain in 24 hours, 48 hours and 7 days between the two groups. Even though there were no statistically significant differences in one-minute and five-minute Apgar scores, neonatal respiratory distress syndrome between the groups neonates of MgSO4 group had more NICU admission which is significant (p value 0.049).: Oral nifedipine is as effective as magnesium sulfate with regard to inhibition of preterm labor.

Acute Tocolysis Using a Single Bolus Dose of Atosiban for Preterm Labor Management: A Prospective Study

Acute Tocolysis Using a Single Bolus Dose of Atosiban for Preterm Labor Management: A Prospective Study

Preterm Labor with Side Effects: Compare the Effectiveness of Magnesium Sulfate (MgSO4) with Isoxsuprine

Background: In India, 25% of pregnancies develop preterm labor (PTL), resulting in 10 to 69% cases of preterm birth. Medical intervention to stop labor, reduce infection rate, and avoid infant respiratory distress has been the subject of studies for a long time. PTL patients usually get tocolytics, corticosteroids, antibiotics, and other clinically symptomatic and supportive therapy to accomplish this goal. Studies further showed that these tocolytic drugs lower intracellular calcium bioavailability via biochemical pathways, hindering the interaction of actin-myosin. Due to the poor success rate of labor arrest, researchers concluded from their studies that widespread adoption of medical management for PTL has been hampered. The high rate of major side effects of tocolytic drugs, particularly beta-mimetic ones, exacerbated this. We know of no clinical evidence on PTL management in India. Objective: The effectiveness and maternal side effects of MgSO4 and isoxsuprine in PTL arrest. Methods: In our study, we included a total of 82 pregnant women who had PTL discomfort and were admitted to the labor department. Both groups were randomly assigned patients. “Group 1 patients received isoxsuprine hydrochloride, whereas group 2 patients received MgSO4”. After that, a comprehensive clinical examination included vital signs, general, systemic, external genitalia, and PV (per vaginal) results. Investigations include CBC, BT, CT, urine full examination, ABO, RH group, serum electrolytes, RBS, vaginal swab, and Renal function test (RFT). Result: Significant difference (p <0.05) indicated that MgSO4 was more effective. Conclusion: MgSO4 can be used as a tocolytic agent in PTL as it shows better tolerance capacity when compared to isoxsuprine.

Acute Tocolysis Using a Single Bolus Dose of Atosiban for Preterm Labor Management: A Prospective Study

Acute Tocolysis Using a Single Bolus Dose of Atosiban for Preterm Labor Management: A Prospective Study

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4–5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.

A Comparison of Nifedipine Versus a Combination of Nifedipine and Sildenafil Citrate in the Management of Preterm Labour.

Background Preterm delivery is a significant contributor to neonatal and infant morbidity and mortality. Preventive methods are preferable to treatment protocols for reducing perinatal mortality and morbidity. The calcium channel blocker nifedipine has the potential to be employed as a tocolytic, whereas the phosphodiesterase inhibitor sildenafil citrate promotes smooth muscle relaxation. Objective This study aims to examine the tocolytic effect of nifedipine in combination with sildenafil citrate in managing preterm labour (PTL). Methods After approval from the ethical board, 160 patients fulfilling the selection criteria were enrolled in the study from the outpatient and emergency department of obstetrics and gynaecology, University of Lahore, Pakistan. After taking written informed consent, their demographic profile, i.e., name, age, gestational age at presentation, parity, and expected date of delivery was noted. Patients were randomly assigned in a 1:1 ratio to two study groups (Group A: sildenafil citrate + nifedipine) and (Group B: nifedipine) using a computer-generated random number table to obtain a trial sequence. In group A, each patient was given nifedipine 20 mg orally, followed by 10 mg orally every eight hours for 48 hours and vaginal administration of sildenafil citrate, 25 mg at eight-hour intervals, for 48 hours. In group B, females were given nifedipine 20 mg orally, followed by 10 mg orally every 8 hours for 48 hours. They were kept admitted for 72 hours.SPSS Statistics version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used to enter and analyse the collected data. Mean and standard deviation was calculated for quantitative variables like age, gestational age at presentation, gestational age at delivery, and BMI. Frequency and percentage were calculated for parity and preterm delivery. Results The study involved 160 patients, with the average age in Group A being 29.60±4.9 years and in Group B being 30.96±4.98 years. In terms of gestational age at delivery, Group A had an average of 34.16±1.7 weeks, while Group B had an average of 33.5±1.8 weeks (p-value<0.05). Preterm delivery was observed in 68.5% of Group A and 41.3% of Group B, with a significant p-value of 0.001. The study also discovered that the duration of prolonged pregnancy was significantly higher in Group A compared to Group B, with averages of 14.96±10.37 days and 10.24±8.97 days, respectively (p-value=0.002). Conclusion The results of this study suggest that the combination of sildenafil citrate and nifedipine may offer a promising new approach to improving pregnancy outcomes in cases of PTL. In the present study, sildenafil citrate plus nifedipine showed a significant effect in the management of PTL and prolongation in mean gestational age at delivery.

Prostaglandin F2α requires activation of calcium-dependent signalling to trigger inflammation in human myometrium.

Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators. Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR. The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling. In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors - NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight into PGF2α pro-inflammatory signalling in term myometrium prior to the onset of labour and suggests that PGF2α signalling pathways could be a potential target for management of preterm labour.

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

BackgroundThere 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.MethodsAdis 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.ResultsThe 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.ConclusionsThis 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.

Pepper fruit (Dennettia tripetala [annonaceae]) seed inhibits uterine contractions via blockade of intracellular calcium release and extracellular calcium influx in ex vivo studies

Dennettia tripetala (DT) is a tree found in rain forest belt of Nigeria, Cameroon and Ivory Coast. The seed is commonly used in preparing food for mothers after delivery because it is believed to play a role in postpartum uterine contraction. There is however no scientific evidence validating this claim. Hence, the study aimed to investigate the effects of DT seed on non-pregnant and pregnant uterus using mouse model. The dried seeds of DT were macerated in methanol and the effects of DT extract were investigated on uterus tissues isolated from non-pregnant and pregnant mice. DT extract was examined on spontaneous uterine contraction, contractions induced by oxytocin, and high potassium chloride (KCl)-induced depolarization. Its effect was also evaluated on calcium ion (Ca2+) release from internal stores. The DT extract suppressed spontaneous uterine contractility in both pregnant and non-pregnant uterus in a concentration-dependent manner. It significantly inhibited uterine contractions elicited by high KCl and oxytocin-induced contractions in both pregnant and non-pregnant uterus. The extract also inhibited uterine contractility induced by oxytocin in the Ca2+-free medium in pregnant and non-pregnant uterus. The study has provided scientific evidence that DT seed extract has uterine relaxing effect in both pregnant and non-pregnant mouse uterus possibly by blocking intracellular Ca2+ released and influx of extracellular Ca2+. The result has shown that DT has no benefit in reducing the risk of post-partum hemorrhage, however, it may have potential benefits in management of dysmenorrhea and preterm labour in non-gravid and gravid uteri respectively.

Effect of nifedipine with and without sildenafil citrate for the management of preterm labor in pregnant women: A randomized clinical trial.

Preterm labor is one of the main causes of neonatal mortality and its treatment is still challenging. The study aimed to compare the effectiveness of nifedipine (Nif) with and without sildenafil citrate (SC) for the treatment of preterm labor in pregnant women. In this clinical trial study, 126 pregnant women referred to the Fatemieh hospital, Hamadan, Iran with a complaint of preterm labor were evaluated. Participants were randomly divided into 2 groups of Nif 20 mg orally (single dose), then 10 mg every 6-hr, and at the same time vaginal SC 25 mg every 8 hr (Nif + SC) or Nif alone. Treatment was continued for 48-72 hr if uterine contractions did not resolve in both groups. Delivery rates at the time of hospitalization and neonatal outcome were compared between the 2 groups. No statistically significant difference was observed between the 2 study groups in terms of mean age, gestational age, body mass index, and parity. 76.2% of Nif + SC participants in the first 72 hr of hospitalization and 57.2% of Nif participants remained without delivery (p = 0.02). The neonatal hospitalization rate of the Nif + SC group in the neonatal intensive care unit was 25.4% and in the Nif group was 42.9% (p = 0.03). Nif with SC is superior to Nif alone in women at risk of preterm labor due to increasing gestational age and better neonatal outcomes.

A Comparative Study of the Effectiveness of Transdermal Nitroglycerine Patches and Oral Nifedipine in Prolongation of Pregnancy in Women With Preterm Labour.

Backgrounds A significant contributor to newborn morbidity and mortality is preterm birth. Several techniques have been employed to identify patients at risk of premature labour. However, these predictors are not always effective because of their multifactorial aetiology. Preterm labour can be suppressed largely through tocolysis. This study compared the effectiveness and safety of transdermal nitroglycerine and oral nifedipine in preventing premature labour. Methods This study was done at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra, from December 2020 to November 2022, on 130 women presenting with preterm labour pains between 28 and 37 weeks of gestational age. All the women selected were randomized into two equal groups by using the envelope method. Sixty-five women were given a nitroglycerine patch (Group A), and the rest (65 women) were given an oral nifedipine tablet (group B). The variables studied were mean days of prolongation of pregnancy, treatment outcome, steroid coverage, along with feto-maternal outcomes among both groups. Results The percentage of women whose pregnancy was prolonged for at least 48 hours in the nitroglycerine group was 75.3%, and in the nifedipine group it was 93.8%. Failure to achieve tocolysis, defined as delivery within 48 hours, was seen significantly more in the nitroglycerine group (24.6%) than in the nifedipine group (6.1%). The overall foetal outcomes were comparable in both groups. Conclusion Oral nifedipine was found to be superior to transdermal nifedipine patches in terms of efficacy and safety in the management of preterm labour, with a better side effect profile.