RESUMO
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 I2 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; 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. 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.
Assuntos
Sulfato de Magnésio , Nifedipino , Nitroglicerina , Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Humanos , Nifedipino/uso terapêutico , Feminino , Gravidez , Trabalho de Parto Prematuro/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Ritodrina/uso terapêutico , Tocolíticos/uso terapêutico , Nitroglicerina/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
Assuntos
Trabalho de Parto Prematuro , Ritodrina , Tocolíticos , Feminino , Humanos , Recém-Nascido , Gravidez , Nifedipino , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/prevenção & controle , Ritodrina/uso terapêutico , Tocólise/métodos , Tocolíticos/efeitos adversos , Estudos ProspectivosRESUMO
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.
Assuntos
Trabalho de Parto Prematuro , Ritodrina , Recém-Nascido , Gravidez , Feminino , Humanos , Ritodrina/uso terapêutico , Mães , Resultado da Gravidez , Estudos Retrospectivos , Gravidez Múltipla , Trabalho de Parto Prematuro/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate whether the short-term tocolysis protocol is as effective as the traditional long-term tocolysis protocol with intravenous ritodrine hydrochloride for preterm labour. STUDY DESIGN: This single-centre, retrospective, observational study was conducted at Kitano Hospital, Osaka, Japan between April 2016 and July 2021. At the study hospital, the management protocol for preterm labour after 26 weeks of gestation was changed from the long-term tocolysis protocol to the short-term tocolysis protocol in November 2019. This study compared patients managed with the two protocols, using propensity score analysis to overcome the potential weaknesses of a retrospective study. The primary outcome was the frequency of preterm birth before 34 weeks of gestation before and after the protocol was revised. The secondary outcomes were frequency of neonatal intensive care unit admission and frequency of neonatal chronic lung disease. RESULTS: The study population consisted of 82 patients managed by the long-term tocolysis protocol and 56 patients managed by the short-term tocolysis protocol. After propensity score-weighted adjustment, the median durations of intravenous ritodrine administration in the long-term and short-term protocols were 18 days and 3 days, respectively. Differences were not detected between the long-term and short-term protocols in terms of the frequency of preterm delivery before 34 weeks of gestation [23.7 % vs 21.6 %, risk ratio (RR) 0.91, 95 % confidence interval (CI) 0.47-1.77], frequency of neonatal intensive care unit admission due to preterm birth (49.5 % vs 39.3 %, RR 0.79, 95 % CI 0.53-1.19) and frequency of neonatal chronic lung disease (4.4 % vs 9.2 %, RR 2.07, 95 % CI 0.51-8.48). CONCLUSION: Using propensity score analysis, changing from the long-term tocolysis protocol to the short-term tocolysis protocol for the management of preterm labour after 26 weeks of gestation did not have a negative effect on the frequency of preterm birth or neonatal prognosis.
Assuntos
Pneumopatias , Trabalho de Parto Prematuro , Nascimento Prematuro , Ritodrina , Tocolíticos , Gravidez , Feminino , Humanos , Recém-Nascido , Ritodrina/uso terapêutico , Nascimento Prematuro/prevenção & controle , Tocolíticos/uso terapêutico , Estudos Retrospectivos , Tocólise/métodos , Pontuação de Propensão , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/prevenção & controleRESUMO
BACKGROUND: Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. METHODS: This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. RESULTS: The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. CONCLUSION: The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.
Assuntos
Ritodrina , Lactente , Recém-Nascido , Feminino , Gravidez , Humanos , Ritodrina/uso terapêutico , Recém-Nascido Prematuro , Sulfato de Magnésio/uso terapêutico , Sulfatos , Estudos de Coortes , Estudos Prospectivos , PotássioRESUMO
BACKGROUND: Treatment with beta-agonist tocolytics preceding external cephalic version (ECV) attempt increases success rates. Most studies have focused on intravenously and orally administered beta-agonists, while other administration routes including intramuscularly (IM) and subcutaneously (SC) are understudied. The aim of this study was to compare the efficacy of IM ritodrine to SC salbutamol given prior to ECV. METHODS: A retrospective study of patients who underwent ECV between 1/2012 and 12/2019 at two medical centers. We compared patients undergoing ECV following IM ritodrine versus SC salbutamol. We matched the two groups by parity and placental location. Maternal, pregnancy, ECV procedure and neonatal characteristics were compared. RESULTS: Overall, 601 women were included in each group. Median maternal age and amniotic fluid index (AFI) were lower in the Ritodrine group (27 vs. 32 years, P<0.001, 11 vs. 15 AFI cm, P<0.001, respectively). The median gestational age at ECV was higher in the Ritodrine group (380/7 vs. 370/7 weeks gestation). Success rate was higher in the Ritodrine group (71.7% vs. 63.8%, P=0.003). Vaginal delivery rate was higher in the Ritodrine group (70.7% vs. 60.1%, P<0.001). The number needed to treat to benefit was 10. In a multivariate analysis, Ritodrine was independently associated with higher ECV success rates as compared with Salbutamol (aOR 2.1, 95%CI 1.52-2.89). CONCLUSIONS: Intramuscular ritodrine significantly improved the success rate of ECV compared to SC salbutamol, and both drugs were safe and acceptable before ECV.
Assuntos
Apresentação Pélvica , Ritodrina , Versão Fetal , Albuterol/uso terapêutico , Apresentação Pélvica/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Placenta , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Ritodrina/uso terapêutico , Versão Fetal/métodosRESUMO
No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses.Impact statementWhat is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors.What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses.What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.
Assuntos
Ressuscitação , Ritodrina , Tocolíticos , Cesárea/efeitos adversos , Feminino , Feto , Frequência Cardíaca Fetal , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Ritodrina/uso terapêutico , Tocólise/métodos , Tocolíticos/efeitos adversosRESUMO
OBJECTIVE: Acute pulmonary edema associated with ritodrine hydrochloride is a rare, life-threatening complication, and dose and duration of ritodrine use are closely associated with this pathology. We report a case of acute pulmonary edema associated with short-duration infusion of ritodrine hydrochloride in a patient with pectus excavatum as an underlying factor. CASE REPORT: A 30-year-old healthy pregnant woman was treated with oral ritodrine for tocolysis between 31 and 35 weeks of pregnancy. At 36 weeks of gestation, she went into preterm labor, with premature rupture of the membrane and breech presentation, and received an infusion of ritodrine hydrochloride for a few hours. Although she was normotensive until labor onset, mild hypertension and proteinuria were recognized. Intraoperatively, a funnel-chest deformity was observed, and she developed postoperative pulmonary edema associated with dyspnea and wet cough and confirmed on chest radiography and arterial gas analysis, and recovered with supportive care. CONCLUSION: Small-dose infusion of ritodrine hydrochloride might cause pulmonary edema in patients with underlying medical problems, including pectus excavatum.
Assuntos
Pulmão/efeitos dos fármacos , Trabalho de Parto Prematuro/prevenção & controle , Edema Pulmonar/induzido quimicamente , Ritodrina/administração & dosagem , Tocolíticos/administração & dosagem , Contração Uterina/efeitos dos fármacos , Adulto , Cesárea , Feminino , Humanos , Infusões Parenterais , Gravidez , Edema Pulmonar/tratamento farmacológico , Ritodrina/efeitos adversos , Ritodrina/uso terapêutico , Tocolíticos/efeitos adversos , Tocolíticos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND Premature labor is an important cause of infant death and long-term disability. This study aimed to explore the safety and effectiveness of combining the tocolytic agents atosiban and ritodrine to extend gestation. MATERIAL AND METHODS The study included 52 patients with late threatened abortion and threatened premature labor between 20°â¸7 and 336â¸7 weeks' gestation who were administrated continuous tocolytic agents for 48 h. Patients were divided into a research group receiving ritodrine combined with atosiban, owing to having no response to ritodrine alone (n=30), and a control group receiving ritodrine alone (n=22). The mean infusion rate and duration of tocolytic administration, gestation extension, pregnancy outcomes, and adverse effects were recorded. Routine blood tests, including C-reactive protein, and cultures for leukorrhea, candida, and mycoplasma were performed before and 1 week after treatment. RESULTS Patients receiving ritodrine with atosiban had a mean gestation extension of 42.53±31.70 days. The extension of gestation of the research group was statistically shorter than that of the control group (P<0.05). The fetal loss rate, newborn birth weight, and Apgar score at 1 min were similar between the 2 groups (all, P>0.05). The research group had a lower incidence of palpitations than the control group (P<0.05). CONCLUSIONS For patients with late threatened abortion or threatened premature labor not controlled with ritodrine alone, ritodrine combined with atosiban extends gestation and improves pregnancy outcomes. For patients with abnormal uterine contractions, routine testing for reproductive tract infection should be performed. When infection is present, anti-infective therapy should be administered.
Assuntos
Ameaça de Aborto/tratamento farmacológico , Trabalho de Parto Prematuro/tratamento farmacológico , Ritodrina/uso terapêutico , Vasotocina/análogos & derivados , Ameaça de Aborto/prevenção & controle , Adulto , Quimioterapia Combinada/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/prevenção & controle , Gravidez , Resultado da Gravidez , Ritodrina/metabolismo , Tocolíticos/efeitos adversos , Tocolíticos/uso terapêutico , Vasotocina/metabolismo , Vasotocina/uso terapêuticoRESUMO
"Trials evaluating tocolytic use in preterm premature rupture of membranes (PPROM) have been small and lacked adequate power to evaluate uncommon outcomes. There still is much controversy on the benefit, length of use, route, and drug of choice among clinicians treating patients with PPROM. Most professional medical societies would propose to consider the use of tocolytics for 48 hours to allow for corticosteroid administration or to allow for maternal transfer to a higher level of care. Longer treatment regimens may lead to adverse maternal and perinatal outcomes. Insufficient data are available to make stronger and more definitive recommendations."
Assuntos
Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Tocolíticos/uso terapêutico , Corticosteroides/uso terapêutico , Feminino , Humanos , Recém-Nascido , Sulfato de Magnésio/uso terapêutico , Gravidez , Nascimento Prematuro/prevenção & controle , Ritodrina/uso terapêutico , Tocólise/métodosRESUMO
Our aim was to evaluate the association between ritodrine and magnesium sulfate (MgSO4) and the occurrence of neonatal hyperkalemia or hypoglycemia among late preterm infants in a retrospective cohort study. We used a nationwide obstetrical database from 2014. A total of 4,622 live preterm infants born at 32-36 gestational weeks participated. Fourteen risk factors based on both clinical relevance and univariate analysis were adjusted in multivariable logistic regression analyses. Neonatal hyperkalemia and hypoglycemia occurred in 7.6% (284/3,732) and 32.4% (1,458/4,501), respectively. Occurrence of hyperkalemia was associated with concomitant usage of ritodrine and MgSO4 compared with no usage (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.09-2.15). Occurrence of hypoglycemia was associated with ritodrine alone (aOR 2.58 [CI 2.21-3.01]) and with concomitant usage of ritodrine and MgSO4 (aOR 2.59 [CI 2.13-3.15]), compared with no usage, and was associated with long-term usage (≥ 48 hours) of ritodrine and cessation directly before delivery. In conclusion, in late preterm infants, usage of ritodrine together with MgSO4 was associated with occurrence of critical neonatal hyperkalemia, and long-term usage of ritodrine and cessation directly before delivery were associated with neonatal hypoglycemia.
Assuntos
Hiperpotassemia/epidemiologia , Hipoglicemia/epidemiologia , Sulfato de Magnésio/efeitos adversos , Ritodrina/efeitos adversos , Adulto , Sinergismo Farmacológico , Feminino , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/patologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/patologia , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/patologia , Recém-Nascido Prematuro , Japão/epidemiologia , Sulfato de Magnésio/uso terapêutico , Trabalho de Parto Prematuro/tratamento farmacológico , Trabalho de Parto Prematuro/patologia , Gravidez , Fatores de Risco , Ritodrina/uso terapêuticoRESUMO
Background We aimed to analyze the success rate of external cephalic version (ECV) for breech presentations performed in our center between March 2011 and March 2016. We evaluated factors related to a successful ECV, delivery mode, complications and newborn status after ECV. Methods Analysis of assembled data of 327 consecutive ECVs in the third trimester was done. Results The total success rate was 56.6%. After a successful ECV, 85.9% of the fetuses were delivered vaginally. Logistic regression analysis of background factors leading to a successful ECV showed that tocolysis with ritodrine and anterior placenta were each significantly correlated with the rate of successful version. No severe complications were registered during the ECVs, and all babies had normal Apgar scores at delivery. Conclusion These findings suggest that attempting an ECV in breech presentations, once or even twice, seems to be an appropriate management given that a successful ECV decreases the rate of cesarean section in this group of patients and by doing so, it might also decrease the risk of cesarean sections in future pregnancies.
Assuntos
Apresentação Pélvica , Cesárea , Ritodrina/uso terapêutico , Versão Fetal , Adulto , Índice de Apgar , Apresentação Pélvica/diagnóstico , Apresentação Pélvica/epidemiologia , Apresentação Pélvica/terapia , Cesárea/métodos , Cesárea/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Prognóstico , Espanha/epidemiologia , Tocolíticos/uso terapêutico , Resultado do Tratamento , Versão Fetal/efeitos adversos , Versão Fetal/métodos , Versão Fetal/estatística & dados numéricosRESUMO
PURPOSE: Phosphodiesterase (PDE) terminates the signaling pathway of myometrial relaxation by degradating cAMP to the inactive 5'-AMP. The PDE4 family is one of the most predominant PDE families that display high affinity to cAMP. The objective of this study was to evaluate the effects of PDE4 gene polymorphisms on tocolytic effects and adverse drug events (ADEs) of ritodrine therapy in patients with preterm labor. METHODS: A total of 170 preterm labor patients were included in this study. To elucidate the effects of genetic polymorphisms on the inter-individual variability of ritodrine efficacy and ADEs, 8 single nucleotide polymorphisms (SNPs) were genotyped: PDE4D (rs1544791, rs983280, rs1504982, rs10940648, rs829259) and PDE4B2 (rs598961, rs2180335, and rs17128809). Additionally, rs1042719 of the ADRB2 gene was included for multivariate analysis. The primary endpoint of this prospective study was the time to delivery (hr). The secondary endpoint was ritodrine-induced ADEs. RESULTS: The mutant-type homozygote carriers of PDE4B2 rs598961 polymorphism showed shorter median time to delivery than those with other genotypes (adjusted hazard ratio 1.6, 95% confidence interval 1.0 to 2.4, P = 0.035). On the other hand, patients with wild-type homozygotes of PDE4B2 rs17128809 showed 2.6~2.9 times higher ADEs compared to those with other genotypes. Among demographic characteristics, gestational age at start of drug therapy and modified Bishop score were significant factors for time to delivery, whereas height, weight, and BSA were significant factors for ritodrine-induced ADEs after adjusting other factors. CONCLUSIONS: This pharmacogenomic study suggested that PDE4 genetic polymorphisms impact individual susceptibility to ß2-adrenergic receptor targeted therapy in patients with preterm labor.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Trabalho de Parto Prematuro/tratamento farmacológico , Ritodrina/uso terapêutico , Tocolíticos/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Feminino , Humanos , Trabalho de Parto Prematuro/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Receptores Adrenérgicos beta 2/genética , Ritodrina/efeitos adversos , Tocolíticos/efeitos adversos , Resultado do TratamentoAssuntos
Contagem de Células Sanguíneas/instrumentação , Diagnóstico Tardio , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Adulto , Cesárea , Citarabina/uso terapêutico , Feminino , Idade Gestacional , Humanos , Isoflavonas/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Trabalho de Parto Prematuro/tratamento farmacológico , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos , Indução de Remissão , Ritodrina/uso terapêuticoRESUMO
BACKGROUND: Antenatal corticosteroid treatment is globally recommended for women at risk of giving birth before 34 weeks of gestation. In Japan, data on the rate of completing recommended antenatal corticosteroid treatment are lacking. This study aimed to: (i) determine the proportion of patients treated for threatened preterm birth with tocolysis who received antenatal glucocorticoids; and (ii) analyze the association between long-term tocolysis and antenatal glucocorticoids treatment as recommended. METHODS: This was a retrospective cohort study using a national inpatient database in Japan. We selected pregnant women who had undergone treatment in hospitals due to threatened preterm birth and received the tocolytic ritodrine hydrochloride by infusion from July 2010 to March 2016, and delivered at < 34 weeks of gestation. The primary outcome was receiving of antenatal glucocorticoid treatment as recommended. Multivariable logistic regression was performed to evaluate factors associated with receiving antenatal glucocorticoid treatment. RESULTS: Only 23% of 4048 eligible patients received glucocorticoid treatment as recommended. Those with longer durations of ritodrine hydrochloride infusion were significantly less likely to receive glucocorticoid treatment as recommended. CONCLUSIONS: In Japan, many patients who receive tocolytic treatment for threatened preterm birth do not receive antenatal glucocorticoid treatment as recommended. Recommended treatment based on apparent evidences should be performed for the patients with threatened preterm birth.
Assuntos
Glucocorticoides/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Nascimento Prematuro/prevenção & controle , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Humanos , Japão , Modelos Logísticos , Análise Multivariada , Guias de Prática Clínica como Assunto , Gravidez , Estudos Retrospectivos , Ritodrina/uso terapêutico , Fatores de Tempo , Tocólise , Tocolíticos/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Ritodrine, a tocolytic ß2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between ß2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine. RESULTS: This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31-15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes. CONCLUSIONS: This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Trabalho de Parto Prematuro/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos beta 2/genética , Ritodrina/uso terapêutico , Administração Intravenosa , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Feminino , Seguimentos , Humanos , Gravidez , Receptores Adrenérgicos beta 2/metabolismo , Ritodrina/administração & dosagemRESUMO
Ritodrine, a drug for the treatment of threatened premature labor, is a highly selective beta-2 agonist with the major metabolites of sulfate and glucuronide conjugates. This study investigated the continuous evaluation of the concentration of ritodrine conjugates in relation to the clinical course in twin pregnancy. The subjects were 9 twin-pregnancy mothers who delivered after receiving ritodrine treatment between April 2012 and December 2013. Serum ritodrine sulfate and glucuronide conjugates were deconjugated using their specific enzymes. Ritodrine concentration was measured by liquid chromatography-tandem mass spectrometry. The continuous infusion rate of ritodrine was 2.66±0.67 (0.8-3.54) µg/min/kg, and the average concentration of unchanged ritodrine was 118.8±33.2 (63.8-194.0) ng/mL. During the study period between week 32 and week 36 of gestation, the average ratio of unchanged ritodrine concentration and sulfate ritodrine conjugate concentration for weeks 32, 33, 34, 35, and 36 were 1.7, 1.9, 1.5, 1.7, and 1.7 not significant (N.S.), respectively. The average ratio of unchanged ritodrine concentration and glucuronide ritodrine conjugate concentration were 1.8, 2.2, 1.9, 1.8, and 2.1 (N.S.), respectively. No statistical difference was identified in the ratios of unchanged ritodrine concentration and sulfate or glucuronide ritodrine conjugate concentrations. Large individual differences were shown in the concentration of sulfate and glucuronide during the gestational period. No change in the ratio of the formation of ritodrine metabolites was identified as the gestational age progressed.
Assuntos
Glucuronídeos/sangue , Gravidez de Gêmeos/sangue , Ritodrina/farmacocinética , Sulfatos/sangue , Agonistas de Receptores Adrenérgicos beta 2 , Adulto , Feminino , Humanos , Trabalho de Parto Prematuro/sangue , Trabalho de Parto Prematuro/prevenção & controle , Gravidez , Ritodrina/sangue , Ritodrina/uso terapêuticoRESUMO
OBJECTIVE: Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total dose of ritodrine hydrochloride prior to delivery and pulmonary oedema in twin pregnancy. We aimed to examine this association and determine the optimal cut-off threshold of total ritodrine hydrochloride dose to predict the incidence of pulmonary oedema in twin pregnancy based on obstetric records. DESIGN: Retrospective cohort study. SETTING: Yamanashi Prefectural Central Hospital, Japan. PARTICIPANTS: Two hundred and twenty-six women with twin pregnancy who delivered at Yamanashi Prefectural Central Hospital between September 2009 and November 2016. METHODS: The obstetric records of the participants were analysed. We defined 1 unit of ritodrine hydrochloride as 72 mg per 24 hours continuous transfusion at 50 µg/min to calculate the dose of ritodrine used for tocolysis. OUTCOME MEASURES: Multivariable logistic regression analysis was performed to examine the association between total dose of ritodrine hydrochloride used for threatened preterm labour and pulmonary oedema, while controlling for potential confounding factors. Then, a receiver-operating characteristic curve was used to determine the optimal cut-off of total ritodrine dose to predict pulmonary oedema incidence. RESULTS: Mean maternal age was 32 (range, 18-46) years; 143 participants were nulliparous (63.3%), 109 had (48.2%) term deliveries and 194 (85.8%) had caesarean deliveries. The overall incidence of pulmonary oedema was 13.7% (31/226). Multivariable analysis showed that the total dose of ritodrine was significantly associated with pulmonary oedema (adjusted OR 1.02; 95% CI 1.004 to 1.03). The best cut-off point to predict the incidence of pulmonary oedema was 26 units (1872 mg) (sensitivity, 61.3%; specificity, 87.8%). CONCLUSION: Our results suggest that consideration of the total dose of ritodrine hydrochloride is helpful in the management of patients with threatened preterm labour in twin pregnancy.