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BMC Pregnancy and Childbirth Apr 2024Some 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. (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Some 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.
OBJECTIVE
To compare the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor.
METHODS
In 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 I index, and publication bias was evaluated by Egger's test.
RESULTS
Forty 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; I: 32.3%). Additionally, there were significant differences between nifedipine and ritodrine (RD, 0.11; 95% CI, 0.02 to 0.21; I, 51.2%) for more than one week RD, 0.10; 95% CI, 0.03 to 0.19; I, 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.
CONCLUSIONS
Considering 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.
Topics: Humans; Nifedipine; Female; Pregnancy; Obstetric Labor, Premature; Magnesium Sulfate; Ritodrine; Tocolytic Agents; Nitroglycerin; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38664622
DOI: 10.1186/s12884-024-06497-w -
BMC Pregnancy and Childbirth Mar 2024Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have...
BACKGROUND
Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma.
CASE PRESENTATION
A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion.
CONCLUSION
Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Adult; Ritodrine; Hydrops Fetalis; Cesarean Section; Placenta; Obstetric Labor, Premature; Hemangioma; Syndrome
PubMed: 38509456
DOI: 10.1186/s12884-024-06391-5 -
Taiwanese Journal of Obstetrics &... Sep 2023To evaluate the safety and efficacy of atosiban and ritodrine in pregnant women who were hospitalized for threatened preterm labor (TPL).
A multicenter, retrospective comparison of pregnancy outcomes between groups of preterm labor nulliparous mothers treated with atosiban vs. ritodrine in singleton and multiple pregnancies.
OBJECTIVE
To evaluate the safety and efficacy of atosiban and ritodrine in pregnant women who were hospitalized for threatened preterm labor (TPL).
MATERIALS AND METHODS
Diagnosis records of preterm labor and subsequent pregnancy-related records and medical records of newborns were extracted from the Clinical Data Warehouse of the Catholic Medical Center's affiliated hospital. Since 2009, cases of preterm labor diagnosed before 34 weeks of pregnancy for first-time mothers who delivered at any one of three hospitals and who received drug treatment for more than 2 days to delay delivery were included in the dataset. Based on characteristics of Korea's national health insurance system, the drug treatment after diagnosis of preterm labor could be classified into cases using only ritodrine (571 women), cases using only atosiban (244 women), and cases where ritodrine treatment was started and then changed to atosiban (275 women). Demographic factors, obstetric outcomes, neonatal outcomes of the two groups were analyzed.
RESULTS
The duration and maintenance of pregnancy were found to be similar between the two groups, although the initial cervical length was significantly shorter in the atosiban cohort (AC). Only in multifetal pregnancies, the maintenance of pregnancy was significantly longer in the AC. The total duration of pregnancy did not show any significant difference between the two groups regardless of singleton or multiple pregnancy. However, the distribution graph showed non-responders in the ritodrine cohort (RC). Our study showed a difference in neonatal birth weight of singleton between the two groups. The length of hospitalization and the NICU admission rate were also significantly higher in the RC for singleton. Although not significant, the proportion of numbers with an Apgar score less than 7 was higher in the RC. Neonatal death was more common in the RG (8 cases in AC and 18 cases in RC).
CONCLUSIONS
Using atosiban for TPL is more effective than using ritodrine for maintaining pregnancy in the case of a multifetal pregnancy. In singleton pregnancies, neonatal outcomes of the atosiban group were superior to those of the ritodrine group. There seems to be a non-responder group when using ritodrine for TPL. Further studies are needed to determine causes of non-responders of ritodrine and effects of ritodrine on the fetus.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Ritodrine; Mothers; Pregnancy Outcome; Retrospective Studies; Pregnancy, Multiple; Obstetric Labor, Premature
PubMed: 37678995
DOI: 10.1016/j.tjog.2023.07.009 -
BMC Medical Research Methodology Aug 2023The Targeted Learning roadmap provides a systematic guide for generating and evaluating real-world evidence (RWE). From a regulatory perspective, RWE arises from diverse... (Observational Study)
Observational Study
BACKGROUND
The Targeted Learning roadmap provides a systematic guide for generating and evaluating real-world evidence (RWE). From a regulatory perspective, RWE arises from diverse sources such as randomized controlled trials that make use of real-world data, observational studies, and other study designs. This paper illustrates a principled approach to assessing the validity and interpretability of RWE.
METHODS
We applied the roadmap to a published observational study of the dose-response association between ritodrine hydrochloride and pulmonary edema among women pregnant with twins in Japan. The goal was to identify barriers to causal effect estimation beyond unmeasured confounding reported by the study's authors, and to explore potential options for overcoming the barriers that robustify results.
RESULTS
Following the roadmap raised issues that led us to formulate alternative causal questions that produced more reliable, interpretable RWE. The process revealed a lack of information in the available data to identify a causal dose-response curve. However, under explicit assumptions the effect of treatment with any amount of ritodrine versus none, albeit a less ambitious parameter, can be estimated from data.
CONCLUSIONS
Before RWE can be used in support of clinical and regulatory decision-making, its quality and reliability must be systematically evaluated. The TL roadmap prescribes how to carry out a thorough, transparent, and realistic assessment of RWE. We recommend this approach be a routine part of any decision-making process.
Topics: Female; Humans; Reproducibility of Results; Research Design; Japan; Randomized Controlled Trials as Topic
PubMed: 37533017
DOI: 10.1186/s12874-023-01998-2 -
Frontiers in Endocrinology 2023It's challenging for healthcare workers to detect neonatal hypoglycemia due to its rapid progression and lack of aura symptoms. This may lead to brain function...
BACKGROUND
It's challenging for healthcare workers to detect neonatal hypoglycemia due to its rapid progression and lack of aura symptoms. This may lead to brain function impairment for the newborn, placing a significant care burden on the family and creating an economic burden for society. Tools for early diagnosis of neonatal hypoglycemia are lacking. This study aimed to identify newborns at high risk of developing neonatal hypoglycemia early by developing a risk prediction model.
METHODS
Using a retrospective design, pairs (470) of women and their newborns in a tertiary hospital from December 2021 to September 2022 were included in this study. Socio-demographic data and clinical data of mothers and newborns were collected. Univariate and multivariate logistic regression were used to screen optimized factors. A neonatal hypoglycemia risk nomogram was constructed using R software, and the calibration curve and receiver operator characteristic curve (ROC) was utilized to evaluate model performance.
RESULTS
Factors integrated into the prediction risk nomogram were maternal age (odds ratio [OR] =1.10, 95% CI: 1.04, 1.17), fasting period (OR=1.07, 95% CI: 1.03, 1.12), ritodrine use (OR=2.00, 95% CI: 1.05, 3.88), gestational diabetes mellitus (OR=2.13, 95% CI: 1.30, 3.50), gestational week (OR=0.80, 95% CI: 0.66, 0.96), fetal distress (OR=1.76, 95% CI: 1.11, 2.79) and neonatal body mass index (OR=1.50, 95% CI: 1.24, 1.84). The area under the curve (AUC) was 0.79 (95% confidence interval [CI]: 0.75, 0.82), specificity was 0.82, and sensitivity was 0.62.
CONCLUSION
The prediction model of this study demonstrated good predictive performance. The development of the model identifies advancing maternal age, an extended fasting period before delivery, ritodrine use, gestational diabetes mellitus diagnosis, fetal distress diagnosis and an increase in neonatal body mass index increase the probability of developing neonatal hypoglycemia, while an extended gestational week reduces the probability of developing neonatal hypoglycemia.
Topics: Pregnancy; Humans; Infant, Newborn; Female; Retrospective Studies; Diabetes, Gestational; Ritodrine; Hypoglycemia; Maternal Age; Infant, Newborn, Diseases; Fetal Diseases
PubMed: 37529595
DOI: 10.3389/fendo.2023.1199628 -
Computational and Structural... 2023Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current...
Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current therapies only delay disease progression and have limited treatment effects. Hence, the development of innovative therapeutic approaches to mitigate the progression of CKD has become an attractive issue. To date, the incidence of CKD is still increasing, and the biomarkers of the pathophysiologic processes of CKD are not clear. Therefore, the identification of novel therapeutic targets associated with the progression of CKD is an attractive issue. It is a critical necessity to discover new therapeutics as nephroprotective strategies to stop CKD progression. In this research, we focus on targeting a prostaglandin E receptor (EP2) as a nephroprotective strategy for the development of additional anti-inflammatory or antifibrotic strategies for CKD. The study identified that ritodrine, dofetilide, dobutamine, and citalopram are highly related to EP2 from the results of chemical database virtual screening. Furthermore, we found that the above four candidate drugs increased the activation of autophagy in human kidney cells, which also reduced the expression level of fibrosis and NLRP3 inflammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflammasome activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.
PubMed: 37484490
DOI: 10.1016/j.csbj.2023.07.007 -
Biomolecules Jun 2023Preterm 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... (Review)
Review
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 β2 adrenergic receptor relax airway smooth muscle and are effective in the treatment of asthma led to the notion that β2 mimetics would prevent preterm birth by relaxing uterine smooth muscle. The activation of cAMP-dependent protein kinase by β2 receptors is unable to provide meaningful tocolysis. The failure of β2 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 β3 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 β2 agonists as tocolytics and suggests a non-canonical signaling role for β3AR in myometrium. The addition of the β3 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 β3 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.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Myometrium; Tocolytic Agents; Premature Birth; Nitric Oxide; Endothelial Cells; Obstetric Labor, Premature; Cyclic AMP-Dependent Protein Kinases; Receptors, Adrenergic
PubMed: 37371585
DOI: 10.3390/biom13061005 -
World Journal of Emergency Medicine 2023
PubMed: 37152524
DOI: 10.5847/wjem.j.1920-8642.2023.043 -
PloS One 2023Prematurity is the foremost cause of death in children under 5 years of age. Genetics contributes to 25-40% of all preterm births (PTB) yet we still need to identify...
Prematurity is the foremost cause of death in children under 5 years of age. Genetics contributes to 25-40% of all preterm births (PTB) yet we still need to identify specific targets for intervention based on genetic pathways. This study involved the effect of region-specific non-synonymous variations and their transcript level mutational impact on protein functioning and stability by various in-silico tools. This investigation identifies potential therapeutic targets to manage the challenge of PTB, corresponding protein cavities and explores their binding interactions with intervening compounds. We searched 20 genes coding 55 PTB proteins from NCBI. Single Nucleotide Polymorphisms (SNPs) of concerned genes were extracted from ENSEMBL, and filtration of exonic variants (non-synonymous) was performed. Several in-silico downstream protein functional effect prediction tools were used to identify damaging variants. Rare coding variants were selected with an allele frequency of ≤1% in 1KGD, further supported by South Asian ALFA frequencies and GTEx gene/tissue expression database. CNN1, COL24A1, IQGAP2 and SLIT2 were identified with 7 rare pathogenic variants found in 17 transcript sequences. The functional impact analyses of rs532147352 (R>H) of CNN1 computed through PhD-SNP, PROVEAN, SNP&GO, PMut and MutPred2 algorithms showed impending deleterious effects, and the presence of this pathogenic mutation in CNN1 resulted in large decrease in protein structural stability (ΔΔG (kcal/mol). After structural protein identification, homology modelling of CNN1, which has been previously reported as a biomarker for the prediction of PTB, was performed, followed by the stereochemical quality checks of the 3D model. Blind docking approach were used to search the binding cavities and molecular interactions with progesterone, ranked with energetic estimations. Molecular interactions of CNN1 with progesterone were investigated through LigPlot 2D. Further, molecular docking experimentation of CNN1 showed the significant interactions at S102, L105, A106, K123, Y124 with five selected PTB-drugs, Allylestrenol (-7.56 kcal/mol), Hydroxyprogesterone caproate (-8.19 kcal/mol), Retosiban (-9.43 kcal/mol), Ritodrine (-7.39 kcal/mol) and Terbutaline (-6.87 kcal/mol). Calponin-1 gene and its molecular interaction analysis could serve as an intervention target for the prevention of PTB.
Topics: Humans; Infant, Newborn; Exons; Genes, Regulator; Molecular Docking Simulation; Premature Birth; Progesterone; Polymorphism, Single Nucleotide
PubMed: 36881567
DOI: 10.1371/journal.pone.0280305