ABSTRACT
Background: Antenatal corticosteroids (ACS) are given to pregnant women at risk of preterm delivery to hasten the maturation of the lungs, lowering the risk of newborn respiratory distress syndrome (RDS) and perinatal mortality. Objective: The aim of this study was to determine whether exposure to ACS was associated with lower rates of perinatal mortality and RDS in preterm infants delivered by women with preterm labour. Methods: This is a secondary analysis of data from four hospitals in Mwanza, Tanzania. All singletons and twins born to women who were in preterm labour between July 2019 and February 2020 and delivered in-hospital between 24 and 34 weeks of gestation were included. Data were recorded from participants' medical records and analysed using STATA Version 14. Results: Over an eight-month period, 588 preterm infants were delivered to 527 women. One hundred and ninety (36.1%) women were given ACS. Infants who were exposed to ACS in utero had a lower rate of perinatal mortality (6.8% vs 19.1%) and RDS (12.3% vs 25.9%) compared to those not exposed to ACS. In adjusted multivariable models, ACS exposure was related to a lower risk of perinatal mortality, aRR 0.23 (95% CI 0.13 - 0.39), and RDS, aRR 0.45 (95% CI 0.30 - 0.68). Conclusion: ACS significantly reduced the risk of perinatal mortality and RDS among preterm infants exposed to ACS in utero and delivered by women in preterm labour. The use of ACS should be encouraged in low-resource settings where preterm birth is prevalent to improve perinatal outcomes.
Subject(s)
Adrenal Cortex Hormones , Obstetric Labor, Premature , Perinatal Mortality , Prenatal Care , Respiratory Distress Syndrome, Newborn , Humans , Female , Pregnancy , Tanzania/epidemiology , Obstetric Labor, Premature/prevention & control , Infant, Newborn , Respiratory Distress Syndrome, Newborn/prevention & control , Respiratory Distress Syndrome, Newborn/epidemiology , Adult , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Prenatal Care/methods , Infant, Premature , Gestational Age , Premature Birth/prevention & control , Premature Birth/epidemiology , Young AdultABSTRACT
Importance: Women with arrested preterm labor (APTL) are at very high risk for spontaneous preterm delivery (SPTD), the leading cause of neonatal mortality and morbidity. To date, no maintenance therapy has been found to be effective for pregnancy prolongation. A few clinical trials with considerable methodological limitations have demonstrated some efficacy for 400 mg vaginal micronized progesterone (VMP) in women with APTL. Objective: To investigate the effectiveness of daily 400 mg VMP for the prolongation of pregnancy after APTL. Design, Setting, and Participants: This randomized clinical trial was conducted between December 19, 2018, and February 27, 2023, in 3 university-affiliated medical centers in Israel. Participants included women with singleton and twin pregnancies after APTL following tocolysis at 24 weeks 0 days to 34 weeks 0 days' gestation. Women with a history of preterm delivery or asymptomatic cervical shortening in the current pregnancy were excluded. Interventions: Participants were randomly allocated to receive VMP 200 mg twice a day or no treatment until 36 weeks 6 days' gestation. Main Outcomes and Measures: The primary end points were mean number of days from study enrollment to delivery and the rate of SPTD prior to 37 weeks' gestation. Results: A total of 129 participants were enrolled (65 in the VMP group and 64 in the no-treatment group). Mean (SD) age was 27.6 (5.1) years. Between the VMP and no-treatment groups, there was no difference in pregnancy prolongation (mean [SD], 40.0 [17.8] vs 37.4 [20.3] days; P = .44) and the rate of SPTD (16 [25%] vs 19 [30%]; relative risk, 0.8; 95% CI, 0.5-1.5; P = .52). In twin pregnancies, including 12 and 15 pairs in the VMP and no-treatment groups, respectively, VMP prolonged pregnancy (mean [SD], 43.7 [18.1] vs 26.1 [15.2] days; P = .02), postponed the delivery week (36.5 [1.4] vs 34.7 [2.2] weeks; P = .01), shortened the length of stay in the neonatal intensive care unit (4.9 [10.6] vs 13.2 [18.5] days; P = .03) and overall hospital stay (8.3 [9.6] vs 15.1 [17.2] days; P = .03), and was associated with a higher birth weight (2444 [528] vs 2018 [430] g; P = .01). Conclusions and Relevance: These findings show that VMP given in a dosage of 200 mg twice a day following APTL is not an effective treatment to prolong pregnancy or prevent SPTD. However, VMP demonstrated beneficial effects in twin pregnancies, warranting further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02430233.
Subject(s)
Obstetric Labor, Premature , Progesterone , Humans , Female , Pregnancy , Progesterone/administration & dosage , Progesterone/therapeutic use , Adult , Administration, Intravaginal , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Premature Birth/prevention & control , Israel , Infant, Newborn , Progestins/administration & dosage , Progestins/therapeutic useABSTRACT
BACKGROUND: Vitamin D deficiency has been suggested to be a risk factor for neonatal respiratory distress syndrome (RDS). This study aimed to evaluate the effect of 25 (OH) D administrations in pregnant women with findings of preterm labor on the incidence of RDS in their preterm neonates. MATERIALS AND METHODS: A randomized controlled clinical trial was conducted on pregnant mothers with gestational age (GA) of less than 34 weeks at risk of preterm delivery. 175 subjects were randomly assigned into two groups, including intervention (intramuscular injection of 50,000 units of 25(OH) D during 72âhours before delivery) and control (no injections). Serum concentrations of 25(OH) D were measured shortly after birth in both mothers and neonates. Then, clinical and laboratory results of mothers and their offspring were recorded (in a checklist). Short-term outcomes and the need for respiratory support were also assessed. Data were analyzed by independent t-test, Mann-Whitney U test, Fisher's exact test, and chi-square test. RESULTS: Even though gestational age, birth weight, delivery method, and serum vitamin D levels are consistent among both groups, 45% of neonates in the control group and 20% in the intervention group developed respiratory distress syndrome (Pâ=â0.05). The mean 25(OH) D level in neonates was 17.7±10.5 and 19.29±9.94âng/mL in the intervention and control groups, respectively (Pâ>â0.05). CONCLUSION: A single dose of 50,000 units of intramuscular 25(OH)D in pregnant women at risk of preterm labor can lower the risk of RDS in the infant.
Subject(s)
Respiratory Distress Syndrome, Newborn , Vitamin D Deficiency , Vitamin D , Humans , Female , Respiratory Distress Syndrome, Newborn/prevention & control , Pregnancy , Infant, Newborn , Vitamin D/blood , Vitamin D/administration & dosage , Vitamin D/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Adult , Infant, Premature , Gestational Age , Obstetric Labor, Premature/prevention & control , Obstetric Labor, Premature/drug therapy , Injections, IntramuscularABSTRACT
This review examines the complexities of preterm birth (PTB), emphasizes the pivotal role of inflammation in the pathogenesis of preterm labor, and assesses current available interventions. Antibiotics, progesterone analogs, mechanical approaches, nonsteroidal anti-inflammatory drugs, and nutritional supplementation demonstrate a limited efficacy. Tocolytic agents, targeting uterine activity and contractility, inadequately prevent PTB by neglecting to act on uteroplacental inflammation. Emerging therapies targeting toll-like receptors, chemokines, and interleukin receptors exhibit promise in mitigating inflammation and preventing PTB.
Subject(s)
Premature Birth , Tocolytic Agents , Humans , Pregnancy , Female , Premature Birth/prevention & control , Tocolytic Agents/therapeutic use , Infant, Newborn , Inflammation/drug therapy , Inflammation/prevention & control , Obstetric Labor, Premature/prevention & controlABSTRACT
AIM: The purpose of this study is to evaluate the oral probiotic effect on pregnancy outcomes in pregnant women undergoing cerclage compared to placebo. METHODS: This study was a double-blind randomized clinical trial undertaken in Yasuj, Iran. 114 eligible participants who have undergone cerclage were randomly divided to either receive probiotic adjuvant or 17α-OHP (250 mg, IM) with placebo from the 16th -37th week of pregnancy by "block" randomization method. Our primary outcomes were preterm labor (PTB) (late and early) and secondary outcomes were other obstetrical and neonatal outcomes included preterm pre-labor rupture of membranes (PPROM), pre-labor rupture of membranes (PROM), mode of delivery, and neonatal outcomes including anthropometric characterize and Apgar score (one and fifth-minute). RESULTS: Results show that there are no statistically significant differences between the two groups in terms of PTB in < 34th (15.51% vs. 17.86%; P = 0.73) and 34-37th weeks of pregnancy (8.7% vs. 16.1%; P = 0.22), and mode of delivery (P = 0.09). PPROM (8.7% vs. 28.5%; P = 0.006) PROM (10.3% vs. 25%; P = 0.04) was significantly lower in patients receiving probiotic adjuvant compared to the control group. After delivery, the findings of the present study showed that there were no significant differences in newborn's weight (3082.46 ± 521.8vs. 2983.89 ± 623.89), head circumstance (36.86 ± 1.53vs. 36.574 ± 1.52), height (45.4 ± 5.34 vs. 47.33 ± 4.92) and Apgar score in one (0.89 ± 0.03 vs. 0.88 ± 0.05) and five minutes (0.99 ± 0.03vs. 0.99 ± 0.03) after birth. CONCLUSION: Our result has shown that the consumption of Lactofem probiotic from the 16th week until 37th of pregnancy can lead to a reduction of complications such as PPROM and PROM.
Subject(s)
Cerclage, Cervical , Pregnancy Outcome , Probiotics , Humans , Pregnancy , Female , Probiotics/therapeutic use , Probiotics/administration & dosage , Double-Blind Method , Adult , Iran , Cerclage, Cervical/methods , Infant, Newborn , Fetal Membranes, Premature Rupture , Young Adult , Premature Birth/prevention & control , Obstetric Labor, Premature/prevention & control , Administration, OralABSTRACT
BACKGROUND: Preterm labor (PTL) is a common and serious pregnancy disorder that can cause long-term neurological issues in the infant. There are conflicting studies concerning whether sildenafil citrate (SC) reduces preterm labor complications. Therefore, the meta-analysis aimed to examine the clinical outcomes in women with threatened PTL who received nifedipine plus SC therapy versus only nifedipine. METHODS: For the original articles, six databases were searched using relevant keywords without restriction on time or language until January 13, 2024. The Cochrane risk-of-bias tool for randomized trials (RoB) and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) were both used to assess the risk of bias in randomized and non-randomized studies, and GRADE determined the quality of our evidence. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULTS: Seven studies with mixed quality were included in the meta-analysis. The study found that combining nifedipine and SC resulted in more prolongation of pregnancy (MD = 6.99, 95% CI: 5.32, 8.65, p < 0.00001), a lower rate of delivery in the 1st to 3rd days after hospitalization (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001), a higher birth weight (252.48 g vs. nifedipine alone, p = 0.02), and the risk ratio of admission to the neonatal intensive care unit (NICU) was significantly lower (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001) compared to nifidepine alone. The evidence was high for prolongation of pregnancy, delivery rate 24-72 h after admission, and NICU admission, but low for newborn birth weight. CONCLUSIONS: Given the effectiveness of SC plus nifedipine in increased prolongation of pregnancy and birth weight, lower delivery in the 1st to 3rd days after hospitalization, and NICU admission, Gynecologists and obstetricians are suggested to consider this strategy for PTL management, although additional article rigor is required to improve the quality of the evidence.
Subject(s)
Drug Therapy, Combination , Nifedipine , Obstetric Labor, Premature , Sildenafil Citrate , Humans , Nifedipine/administration & dosage , Nifedipine/therapeutic use , Sildenafil Citrate/administration & dosage , Sildenafil Citrate/therapeutic use , Female , Pregnancy , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Infant, Newborn , Tocolytic Agents/administration & dosage , Tocolytic Agents/therapeutic use , Treatment OutcomeABSTRACT
In brief: Preterm birth is the leading cause of perinatal morbidity and mortality, and new therapies that delay preterm birth and improve neonatal outcomes are urgently needed. This study investigates whether ticagrelor inhibits uterine contractility and inflammation in preclinical in vitro, ex vivo (human) and in vivo (mouse) studies, to explore the potential of repurposing ticagrelor for the prevention of preterm birth. Abstract: Preterm birth remains a significant global health challenge, affecting approximately 10% of pregnancies and resulting in one million deaths globally every year. Tocolytic agents, used to manage preterm labour, have considerable limitations including lack of efficacy, and adverse side effects, emphasising the urgent need for innovative solutions. Here, we explore repurposing an antiplatelet cardioprotective drug, ticagrelor, as a potential treatment to prevent preterm birth. Ticagrelor has demonstrated pleiotropic actions beyond platelet inhibition, including relaxant effects on smooth muscle cells and anti-inflammatory effects in models of diabetes and sepsis. As preterm birth is underscored by inflammatory processes triggering uterine contractions, these actions position ticagrelor as an attractive candidate for prevention or delay of preterm birth. Utilising primary human myometrial tissue, human myometrial cells, and a mouse model of preterm birth, we investigated ticagrelor's potential as a safe and effective therapy for preterm birth. We showed that ticagrelor did not reduce the frequency or strength of spontaneous muscle contractions of ex vivo myometrial tissue nor did it reduce in vitro inflammation-induced contractility in myometrial cells. Additionally, ticagrelor did not exhibit the anticipated anti-inflammatory effects in myometrial cell culture experiments. In our mouse model of preterm birth, ticagrelor neither improved the preterm birth rate or fetal survival outcomes. Gene expression of pro-inflammatory cytokines and contraction-associated proteins in postpartum mouse uteri were unaltered by ticagrelor. In conclusion, ticagrelor is not a strong candidate to continue investigations in clinical trial for the treatment of preterm labour and prevention of preterm birth.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Animals , Mice , Premature Birth/prevention & control , Premature Birth/metabolism , Ticagrelor/pharmacology , Ticagrelor/metabolism , Ticagrelor/therapeutic use , Obstetric Labor, Premature/prevention & control , Obstetric Labor, Premature/metabolism , Myometrium/metabolism , Inflammation/metabolism , Anti-Inflammatory Agents/pharmacologyABSTRACT
In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with an intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (Ctrough ) was 22.6 ± 17.3 ng/mL, the maximum plasma concentration (Cmax ) was 30.9 ± 15.3 ng/mL and the time to maximum concentration (Tmax ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUCtau ) was 152.3 ± 91.8 mg/Lã»h, and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUCtau of nifedipine can predict term delivery. The AUCtau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.
Subject(s)
Obstetric Labor, Premature , Ritodrine , Tocolytic Agents , Female , Humans , Infant, Newborn , Pregnancy , Nifedipine , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Ritodrine/therapeutic use , Tocolysis/methods , Tocolytic Agents/adverse effects , Prospective StudiesABSTRACT
This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the management of preterm labor. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of examinations with the aim to improve the accuracy in diagnosing preterm labor and allow timely and appropriate administration of tocolytics, antenatal corticosteroids and magnesium sulphate and avoid unnecessary or excessive interventions. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world in the light of scientific literature and serves as a guideline for use in clinical practice.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Tocolytic Agents , Infant, Newborn , Female , Pregnancy , Humans , Obstetric Labor, Premature/diagnosis , Obstetric Labor, Premature/prevention & control , Tocolytic Agents/therapeutic use , Magnesium Sulfate/therapeutic useABSTRACT
Preterm labor occurs in around 10% of pregnancies worldwide. Once diagnosed, significant efforts must be made to reduce the likelihood of morbidity and mortality associated with preterm birth. In high-resource settings, access to hospitals with a neonatal intensive care unit (NICU) is readily available, whereas access to NICU care is limited in low- and middle-income countries (LMICs) and many rural settings. Use of FIGO's Prep-for-Labor triage method rapidly identifies low- and high-risk patients with preterm labor to enable clinicians to decide whether the patient can be managed on site or if transfer to a level II-IV facility is needed. The management steps described in this paper aim to minimize the morbidity and mortality associated with preterm labor and in the setting of preterm labor with preterm premature rupture of membranes (PPROM). The methods for accurate diagnosis of PPROM and chorioamnionitis are described. When the risk of preterm birth is high, antenatal corticosteroids should be administered for lung maturation combined with limited tocolysis for 48 hours to permit the corticosteroid course to be completed. Magnesium sulfate is also administered for fetal neuroprotection. Implementation of FIGO's Prep-for-Labor triage method in an LMIC setting will help improve maternal and neonatal outcomes.
Subject(s)
Fetal Membranes, Premature Rupture , Obstetric Labor, Premature , Premature Birth , Pregnancy , Infant, Newborn , Humans , Female , Premature Birth/prevention & control , Triage , Obstetric Labor, Premature/diagnosis , Obstetric Labor, Premature/prevention & control , Fetal Membranes, Premature Rupture/diagnosis , Fetal Membranes, Premature Rupture/therapy , Adrenal Cortex Hormones/therapeutic useABSTRACT
PURPOSE: Preterm birth is increasing, and obstetric nurses should have the competency to provide timely care. Therefore, training is necessary in the maternal nursing practicum. This study aimed to investigate the effects of practice education using a preterm-labor assessment algorithm on preterm labor-related knowledge and clinical practice confidence in senior nursing students. METHODS: A pre-post quasi-experimental design with three groups was used for 61 students. The preterm-labor assessment algorithm was modified into three modules from the preterm-labor assessment algorithm by March of Dimes. We evaluated preterm labor-related knowledge, clinical practice confidence, and educational satisfaction. Data were analyzed with the paired t-test and repeated-measures analysis of variance. RESULTS: The practice education using a preterm-labor assessment algorithm significantly improved both preterm labor-related knowledge and clinical practice confidence (paired t=-7.17, p<.001; paired t=-5.51, p<.001, respectively). The effects of the practice education using a preterm-labor assessment algorithm on knowledge lasted until 8 weeks but decreased significantly at 11 and 13 weeks after the program, while the clinical practice confidence significantly decreased at 8 weeks post-program. CONCLUSION: The practice education using a preterm-labor assessment algorithm was effective in improving preterm labor-related knowledge and clinical practice confidence. The findings suggest that follow-up education should be conducted at 8 weeks, or as soon as possible thereafter, to maintain knowledge and clinical confidence, and the effects should be evaluated.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Pregnancy , Female , Humans , Infant, Newborn , Obstetric Labor, Premature/prevention & control , Mental Processes , Personal Satisfaction , AlgorithmsABSTRACT
BACKGROUND: Preterm labor is one of the most important causes of hospitalization during pregnancy and can lead to serious complications in neonates. OBJECTIVE: This study aims to compare the effect of transdermal nitroglycerin (TNG) patches and sublingual tablets of Isosorbide dinitrate (ISD) for the prevention of preterm delivery. METHODS: A total of 110 healthy pregnant women aged 18-35 years with a healthy and alive fetus and gestational age between 24-34 weeks who had at least 8 regular uterine contractions per hour were included in this single-blinded clinical trial. After exclusion, the women were randomly divided into TNG (n = 50) and ISD (n = 49) groups. After the first dose of medication (TNG or ISD), patients who developed complications such as hypotension, headache, or both, were also excluded from the study. RESULTS: A total of 58 patients completed the treatment course (29 patients in each group). A significant difference in delayed preterm labor and recovery time was reported between the TNG and ISD groups. CONCLUSION: Complications and the number of contractions were not statistically different in the two groups. We concluded that the TNG patch is more effective than ISD in delaying labor. Both drugs are likely to have a similar incidence of side effects.
Subject(s)
Hypotension , Obstetric Labor, Premature , Infant, Newborn , Humans , Female , Pregnancy , Infant , Nitroglycerin/pharmacology , Nitroglycerin/therapeutic use , Isosorbide Dinitrate/pharmacology , Isosorbide Dinitrate/therapeutic use , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Administration, OralABSTRACT
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.
Subject(s)
Fatty Acids, Omega-3 , Obstetric Labor, Premature , Premature Birth , Infant, Newborn , Female , Humans , Premature Birth/prevention & control , Progesterone , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & controlABSTRACT
Preterm labor leading to preterm birth is the leading cause of infant morbidity and mortality. At the present time, nothing can reliably halt labor once it begins. The knowledge that agonists of the ß2 adrenergic receptor relax airway smooth muscle and are effective in the treatment of asthma led to the notion that ß2 mimetics would prevent preterm birth by relaxing uterine smooth muscle. The activation of cAMP-dependent protein kinase by ß2 receptors is unable to provide meaningful tocolysis. The failure of ß2 agonists such as ritodrine and terbutaline to prevent preterm birth suggests that the regulation of uterine smooth muscle is disparate from that of airway. Other smooth muscle quiescent-mediating molecules, such as nitric oxide, relax vascular smooth muscle in a cGMP-protein kinase G-dependent manner; however, nitric oxide activation of protein kinase G fails to explain the relaxation of the myometrium to nitric oxide. Moreover, nitric oxide-mediated relaxation is blunted in preterm labor, and thus, for this reason and because of the fall in maternal blood pressure, nitric oxide cannot be employed as a tocolytic. The ß3 adrenergic receptor-mediated relaxation of the human myometrium is claimed to be cAMP-dependent protein kinase-dependent. This is scientifically displeasing given the failure of ß2 agonists as tocolytics and suggests a non-canonical signaling role for ß3AR in myometrium. The addition of the ß3 agonist mirabegron to pregnant human myometrial strips in the tissue bath relaxes oxytocin-induced contractions. Mirabegron stimulates nitric oxide production in myometrial microvascular endothelial cells, and the relaxation of uterine tissue in vitro is partially blocked by the addition of the endothelial nitric oxide synthase blocker Nω-Nitro-L-arginine. Recent data suggest that both endothelial and smooth muscle cells respond to ß3 stimulation and contribute to relaxation through disparate signaling pathways. The repurposing of approved medications such as mirabegron (Mybetriq™) tested in human myometrium as uterine tocolytics can advance the prevention of preterm birth.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Tocolytic Agents , Infant, Newborn , Pregnancy , Female , Humans , Myometrium/metabolism , Tocolytic Agents/pharmacology , Tocolytic Agents/metabolism , Tocolytic Agents/therapeutic use , Premature Birth/prevention & control , Nitric Oxide/metabolism , Endothelial Cells/metabolism , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Obstetric Labor, Premature/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Receptors, Adrenergic/metabolismABSTRACT
OBJECTIVES: To evaluate the timing of antenatal corticosteroids (ACS) administration in relation to the delivery timing based on indications and risk factors for preterm delivery. METHODS: We conducted a retrospective cohort study to understand what factors predict the optimal timing of ACS administration (ACS administration within seven days). We reviewed consecutive charts of adult pregnant women receiving ACS from January 1, 2011, to December 31, 2019. We excluded pregnancies under 23 weeks, incomplete and duplicate records, and patients delivered outside our health system. The timing of ACS administration was categorized as optimal or suboptimal. These groups were analyzed regarding demographics, indications for ACS administration, risk factors for preterm delivery, and signs and symptoms of preterm labor. RESULTS: We identified 25,776 deliveries. ACS were administered to 531 pregnancies, of which 478 met the inclusion criteria. Of the 478 pregnancies included in the study, 266 (55.6â¯%) were delivered in the optimal timeframe. There was a higher proportion of patients receiving ACS for the indication of threatened preterm labor in the suboptimal group as compared to the optimal group (85.4â¯% vs. 63.5â¯%, p<0.001). In addition, patients who delivered in the suboptimal timeframe had a higher proportion of short cervix (33â¯% vs. 6.4â¯%, p<0.001) and positive fetal fibronectin (19.8â¯% vs. 1.1â¯%, p<0.001) compared to those who delivered in the optimal timeframe. CONCLUSIONS: More emphasis should be placed on the judicious use of ACS. Emphasis should be placed on clinical assessment rather than relying solely on imaging and laboratory tests. Re-appraisal of institutional practices and thoughtful ACS administration based on the risk-benefit ratio is warranted.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Adult , Infant, Newborn , Female , Humans , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Retrospective Studies , Prenatal Care/methods , Adrenal Cortex Hormones/adverse effects , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & controlABSTRACT
OBJECTIVE: To assess the incidence of threatened preterm labor and preterm labor admissions and treatment of women with singleton gestations and no prior preterm birth before and after implementation of the universal mid-trimester transvaginal ultrasound cervical length screening. MATERIALS AND METHODS: A retrospective cohort study included of singleton gestations without a history of preterm birth presenting with threatened preterm labor between 24 0/7 and 36 6/7 gestational week in two study periods: before and after the implementation of the universal cervical length screening. Women with cervical length <25 mm were considered being at high risk for preterm birth and were prescribed a treatment with vaginal progesterone daily. The primary outcome was the incidence of threatened preterm labor. Secondary outcomes were the incidence of preterm labor. RESULTS: We have found a significant increase in the incidence of threatened preterm labor from 6.42% (410/6378) in 2011 to 11.61% (483/4158) in 2018 (p < 0.0001). Gestational age at triage consult was lower in than in 2011, although the rate of admission for threatened preterm labor was similar in both periods. There was a significant decrease in the incidence of preterm delivery <37 weeks from 25.60% in 2011 to 15.94% in 2018 (p < 0.0004). Although there was a reduction in preterm delivery ≤34 weeks, this reduction was not significant. CONCLUSION: The universal mid-trimester cervical length screening in asymptomatic women is not associated with a reduction in the frequency of threatened preterm labor or the admission rate for preterm labor, but reduces the rate of preterm births.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Premature Birth/epidemiology , Premature Birth/prevention & control , Retrospective Studies , Obstetric Labor, Premature/epidemiology , Obstetric Labor, Premature/prevention & control , Pregnancy Trimester, Second , Cervix Uteri/diagnostic imaging , Cervical Length MeasurementABSTRACT
We conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy of oral dydrogesterone (DG) on maternal and neonatal consequences in the treatment of preterm labor. We included 100 nulliparous mothers (24-34 weeks) with normal pregnancy who had preterm labor pain. Participants who received magnesium sulfate were randomly assigned to the investigation group (DG 30 mg/day) or placebo group. Maternal and neonatal outcomes were compared between the two groups. Recurrent uterine contraction (UC) rates (92% vs. 88%, P = 0.862) and the incidence of preterm delivery (66% vs. 58%, P = 0.834) were not different in the DG and placebo groups. No significant differences were observed in terms of gestational age at delivery (33.5 ± 3.5 vs. 34.2 ± 3.2, P = 0.281), latency period (5.53 ± 2.29 days vs. 5.59 ± 2.57 days, P = 0.622), cervical dilation (1.82 ± 0.26 cm vs. 1.84 ± 0.29 cm, P = 0.281), and effacement (53 ± 4.47% vs. 57.21 ± 6.27%, P = 0.622) between the placebo and DG groups. The percentage of neonates with a 1-min Apgar score < 7 was higher in the placebo group compared with that of the DG group (12% vs. 0%, P = 0.0001). However, both groups were similar in the frequency of a 5-min Apgar score < 7. No differences in the term of adverse effects of medications were recorded. Our results showed that DG adjuvant to magnesium sulfate could not be effective in improving the incidence of preterm labor, rate of recurrent UC, latency period, pregnancy outcomes, and maternal and neonatal outcomes when compared with the placebo group.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Dydrogesterone/therapeutic use , Obstetric Labor, Premature/prevention & control , Premature Birth/prevention & control , Pregnancy Outcome , Uterine Contraction , Magnesium Sulfate , Double-Blind MethodABSTRACT
BACKGROUND: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. OBJECTIVES: To assess effectiveness of progestogen maintenance therapy after an episode of PTL. SEARCH STRATEGY: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed. SELECTION CRITERIA: Randomised controlled trials (RCT) investigating women between 16+0 and 37+0 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group. DATA COLLECTION AND ANALYSIS: Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias. MAIN RESULTS: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40-8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99-239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI -4.55 to 9.42). CONCLUSIONS: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended.
Subject(s)
Obstetric Labor, Premature , Premature Birth , Tocolytic Agents , Pregnancy , Infant, Newborn , Female , Humans , Progestins/therapeutic use , Tocolytic Agents/therapeutic use , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Premature Birth/prevention & control , Premature Birth/drug therapy , Birth WeightABSTRACT
BACKGROUND: Preterm delivery is considered the leading cause of mortality worldwide in children under 5 years old. Approximately 45 million pregnant women are hospitalized yearly for threatened preterm labor. However, only 50% of pregnancies complicated by threatened preterm labor end in delivery before the estimated date, classifying the rest as false threatened preterm labor. The ability of current diagnostic methods to predict threatened preterm labor is low (low positive predictive value), ranging between 8% and 30%. This highlights the need for a solution that accurately detects and differentiates between false and real threatened preterm labors in women who attend obstetrical clinics and hospital emergency departments with delivery symptoms. OBJECTIVE: Primarily, this aimed to assess the reproducibility and usability of a novel medical device, the Fine Birth, aimed at accurately diagnosing threatened preterm labor through the objective quantification of pregnant women's cervical consistency. Secondarily, this study aimed to evaluate the effect of training and the incorporation of a lateral microcamera on the device's reliability and usability outcomes. STUDY DESIGN: A total of 77 singleton pregnant women were recruited during their follow-up visits to the obstetrical and gynecologic departments at 5 Spanish hospitals. The eligibility criteria included pregnant women aged ≥18 years; women with a normal fetus and uncomplicated pregnancy; women without prolapse of membranes, uterine anomalies, previous cervical surgery, or latex allergy; and women signing the informed written consent. Cervical tissue stiffness was assessed using the Fine Birth device, whose technology is based on the propagation of torsional waves through the studied tissue. Cervical consistency measurements were taken for each woman until obtaining 2 valid measurements by 2 different operators. The intraobserver and interobserver reproducibilities of the Fine Birth measurements were assessed using the intraclass correlation coefficients with a 95% confidence interval and the Fisher test P value. The usability was evaluated on the basis of the clinicians' and participants' feedback. RESULTS: There was good intraobserver reproducibility (intraclass correlation coefficient, 0.88; 95% confidence interval, 0.84-0.95; Fisher test P value<.05). As the results obtained for the interobserver reproducibility did not reach the desired acceptable values (intraclass correlation coefficient of <0.75), a lateral microcamera was added to the Fine Birth intravaginal probe, and the operators involved in the clinical investigation received the corresponding training with the modified device. The analysis of 16 additional subjects demonstrated excellent interobserver reproducibility (intraclass correlation coefficient, 0.93; 95% confidence interval, 0.78-0.97) and an improvement after the intervention (P<.0001). CONCLUSION: The robust reproducibility and usability results obtained after the insertion of a lateral microcamera and the corresponding training make the Fine Birth a promising novel device to objectively quantify the patient's cervical consistency, diagnose threatened preterm labor, and, thus, predict the risk of spontaneous preterm birth. Further research is needed to demonstrate the clinical utility of the device.