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Obstetrics & Gynecology Science Sep 2022The external cephalic version (ECV) has been shown to lower the likelihood of cesarean section requirements among pregnant women with breech presentations. In the...
OBJECTIVE
The external cephalic version (ECV) has been shown to lower the likelihood of cesarean section requirements among pregnant women with breech presentations. In the current study, we investigated the effectiveness and safety of ritodrine as a tocolytic for ECV.
METHODS
A total of 407 pregnant women with breech presentations, who had no contraindications for ECV, were enrolled in this study. Multivariable logistic regression analyses were used to assess the impact of ritodrine use on the safety and efficacy of ECV.
RESULTS
The overall success rate was 67.6%, and ritodrine use was associated with significantly higher odds of successful ECV after adjusting for confounders. Moreover, using ritodrine did not increase the risk of adverse effects, including temporary changes in fetal heart rate, need for elective or emergency cesarean section due to fetal distress during ECV, low Apgar scores, and perinatal mortality.
CONCLUSION
Our results suggest that using ritodrine as a tocolytic during ECV may increase the likelihood of ECV success and may not increase adverse perinatal outcomes.
PubMed: 35908652
DOI: 10.5468/ogs.22106 -
BMC Pregnancy and Childbirth Jan 2023Ritodrine hydrochloride, a β2-adrenergic agonist, has been widely used in Asia and Europe to treat preterm labor in pregnant women. It has some typical side effects,... (Review)
Review
BACKGROUND
Ritodrine hydrochloride, a β2-adrenergic agonist, has been widely used in Asia and Europe to treat preterm labor in pregnant women. It has some typical side effects, such as palpitations, pulmonary edema, and hypokalemia. Here, we report a case of rhabdomyolysis and psychiatric symptoms might be associated with intravenous ritodrine.
CASE PRESENTATION
A 32-year-old Chinese primigravida woman who was pregnant with twins by in vitro fertilization-embryo transfer was diagnosed with placenta previa and threatened abortion at 21 gestational weeks (GW). The patient was then treated with ritodrine hydrochloride. The initial dose of ritodrine was 150 μg/min, gradually increasing to 360 μg/min at 23 GW and 400 μg/min at 27 GW. Magnesium sulfate was added to the ritodrine regimen at 21 GW in dosage of 1-2 g/h. Psychiatric symptoms appeared at 24, 26, and 27 GW, manifesting as depression, anxiety, and suicidal tendencies. Severe muscle pain in her limbs and general weakness appeared after six weeks of ritodrine administration, which might have been a sign of rhabdomyolysis resulting from ritodrine administration. After ceasing the administration of ritodrine, the muscle pain and relevant data from laboratory tests on the patient were significantly improved, and her mood was stable. It is worth noting that this is the first time to report psychiatric symptoms may associated with the administration of ritodrine. In addition, we reviewed and analyzed six reported cases of rhabdomyolysis caused by ritodrine.
CONCLUSION
Our results suggest that we should pay more attention to the risk of rhabdomyolysis and psychiatric symptoms induced by intravenous ritodrine hydrochloride, especially in patients with a history of neuromuscular disorder, or concomitant use of magnesium sulfate.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Adult; Ritodrine; Tocolytic Agents; Magnesium Sulfate; Myalgia; Rhabdomyolysis
PubMed: 36611175
DOI: 10.1186/s12884-022-05299-2 -
Obstetrics & Gynecology Science Jan 2018In terms of efficacy, several previous studies have shown that the success rate in inhibiting preterm labor was not different between magnesium sulfate and ritodrine....
OBJECTIVE
In terms of efficacy, several previous studies have shown that the success rate in inhibiting preterm labor was not different between magnesium sulfate and ritodrine. However, there is a paucity of information regarding the efficacy of both medications after consideration of intra-amniotic infection, which is one of the most important prognostic factors in patients of threatened preterm birth. The objective of this study was to compare the efficacy and safety of magnesium sulfate with that of ritodrine in preterm labor.
METHODS
In this retrospective cohort study, we included patients who were admitted and treated with either ritodrine or magnesium sulfate with the diagnosis of preterm labor at 24-33.6 weeks of gestational age between January 2005 to April 2015. Patients were divided into 2 groups according to the first-used tocolytics (ritodrine group and magnesium sulfate group). We compared the efficacy and prevalence of side effect in each group. The efficacy of both tocolytics was evaluated in terms of preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need for 2nd line therapy.
RESULTS
A total number of 201 patients were enrolled including 177 cases in ritodrine group and 24 cases in magnesium sulfate group. The efficacy of both tocolytics (preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need for 2nd line therapy) was not different between the 2 groups of cases. In multivariate analysis, gestational age at treatment, twin gestation, intra-amniotic infection and maternal C-reactive protein (CRP) was associated with treatment failure (preterm delivery within 48 hours), but the type of tocolytics was not significantly associated with treatment failure. The type of side effect was different in the 2 groups, but the frequency of total adverse effect, need for discontinuation of therapy because of maternal adverse effect, and severe adverse effect were not different between the two groups of cases.
CONCLUSION
The efficacy and safety of magnesium sulfate was similar to ritodrine, and can be a substitute tocolytics. Additionally, failure of tocolytic therapy was determined by gestational age at treatment, twin gestation, intra-amniotic infection, and maternal CRP, not by the type of tocolytics.
PubMed: 29372151
DOI: 10.5468/ogs.2018.61.1.63 -
PloS One 2020Ritodrine is one of the most commonly used tocolytics in preterm labor, acting as a ß2-adrenergic agonist that reduces intracellular calcium levels and prevents...
INTRODUCTION
Ritodrine is one of the most commonly used tocolytics in preterm labor, acting as a ß2-adrenergic agonist that reduces intracellular calcium levels and prevents myometrial activation. Ritodrine infusion can result in serious maternal complications, and pulmonary edema is a particular concern among these. The cause of pulmonary edema following ritodrine treatment is multifactorial; however, the contributing genetic factors remain poorly understood. This study investigates the genetic variants associated with ritodrine-induced pulmonary edema.
METHODS
In this case-control study, 16 patients who developed pulmonary edema during ritodrine infusion [case], and 16 pregnant women who were treated with ritodrine and did not develop pulmonary edema [control] were included. The control pregnant women were selected after matching for plurality and gestational age at the time of tocolytic use. Maternal blood was collected during admission for tocolytic treatment, and whole exome sequencing was performed with the stored blood samples.
RESULTS
Gene-wise variant burden (GVB) analysis resulted in a total of 71 candidate genes by comparing the cumulative effects of multiple coding variants for 19729 protein-coding genes between the patients with pulmonary edema and the matched controls. Subsequent data analysis selected only the statistically significant and deleterious variants compatible with ritodrine-induced pulmonary edema. Two final candidate variants in CPT2 and ADRA1A were confirmed by Sanger sequencing.
CONCLUSIONS
We identified new potential variants in genes that play a role in cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) regulation, which supports their putative involvement in the predisposition to ritodrine-induced pulmonary edema in pregnant women.
Topics: Adult; Case-Control Studies; Female; Genetic Variation; Humans; Myometrium; Obstetric Labor, Premature; Pregnancy; Pulmonary Edema; Ritodrine; Tocolytic Agents
PubMed: 33166306
DOI: 10.1371/journal.pone.0241215 -
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 -
American Journal of Translational... 2022To explore the efficacy of Atosiban combined with Ritodrine treatment on spontaneous threatened preterm birth and its effect on platelet-activating factor (PAF) and...
OBJECTIVE
To explore the efficacy of Atosiban combined with Ritodrine treatment on spontaneous threatened preterm birth and its effect on platelet-activating factor (PAF) and fetal fibronectin levels.
METHODS
Medical records from 120 patients with threatened preterm birth admitted to Baoji Maternal and Child Health Hospital from October 2020 to December 2021 were collected for this retrospective analysis. A total of 56 patients treated with Ritodrine alone were taken as the control group (CG), and the other 64 patients given combined treatment of Atosiban and Ritodrine were seen as the observation group (OG). Indexes of uterine contraction inhibition rate, pregnancy prolongation time, onset time, adverse reactions and pregnancy outcomes were compared between the two groups; in addition, the levels of inflammatory factors as well as PAF and fFN before and after treatment were detected and compared between two groups.
RESULTS
Compared with the CG, the uterine contraction inhibition rate as well as the pregnancy prolongation time in the OG were evidently higher (all P<0.05); the time of the disappearance of uterine contraction in the OG was significantly shorter (P<0.05); the rate of full-term delivery and neonatal 1-min Apgar score in the OG were obviously higher (P<0.05); and the incidence of total adverse reactions in the OG was markedly lower (P<0.05). However, there was no significant difference observed in the neonatal asphyxia rate and the number of fetuses between the two groups (P>0.05). After treatment, the OG was observed with markedly lower level of inflammatory factors C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) than the CG (P<0.05); levels of PAF and fFN decreased significantly in both two groups (P<0.05), and the levels in the OG were comparatively lower as compared to the CG (P<0.05). The areas under the ROC curve for PAF and fFN to predict pregnancy outcome were 0.766 and 0.757, respectively.
CONCLUSION
Atosiban combined with Ritodrine evidently improves the therapeutic efficacy in patients with threatened preterm labor, reduces the occurrence of adverse pregnancy outcomes as well as the levels of PAF and fFN.
PubMed: 36505338
DOI: No ID Found -
Case Reports in Obstetrics and... 2020Ritodrine hydrochloride is used for preterm labor, although serious side effects, including agranulocytosis, are reported. We report a case of ritodrine...
Ritodrine hydrochloride is used for preterm labor, although serious side effects, including agranulocytosis, are reported. We report a case of ritodrine hydrochloride-induced agranulocytosis accompanied by bacteremia due to catheter infection. At 24 weeks of gestation, a female patient presented due to threatened premature labor and was administered continuous intravenous infusion of ritodrine hydrochloride. On day 36 after starting intravenous ritodrine hydrochloride, she was diagnosed with agranulocytosis. The white blood cell and granulocyte count nadirs were 1,660/l and 438/l. The cumulative dose of ritodrine hydrochloride was 2,610 mg. Ritodrine therapy was immediately stopped, and she was given an intravenous injection of antibiotics and granulocyte colony-stimulating factor. From her blood culture, methicillin-sensitive was detected. However, she started vaginal delivery two days after we stopped the ritodrine infusion. When using ritodrine hydrochloride, it is necessary to frequently check the white blood cell count, regardless of the total dose and treatment period.
PubMed: 32832175
DOI: 10.1155/2020/5846161 -
Biological & Pharmaceutical Bulletin 2017Ritodrine, 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....
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.
Topics: Adrenergic beta-2 Receptor Agonists; Adult; Female; Glucuronides; Humans; Obstetric Labor, Premature; Pregnancy; Pregnancy, Twin; Ritodrine; Sulfates
PubMed: 28566635
DOI: 10.1248/bpb.b16-00818 -
Scientific Reports Jan 2021Beta-2 adrenergic receptor (B2AR) agonists, used as asthma treatments and tocolytics during pregnancy, have recently been reported to be associated with autism in their...
Beta-2 adrenergic receptor (B2AR) agonists, used as asthma treatments and tocolytics during pregnancy, have recently been reported to be associated with autism in their offspring. However, the particular link between autism and ritodrine, a common type of B2AR agonist used solely as tocolytics, has never been substantiated with any nationwide database. Thus, we aimed to examine the association between in utero exposure of ritodrine and the risk of autism in their offspring using a national database. This population-based cohort study was conducted by merging the Korea National Health Insurance claims database and National Health Screening Program for Infants and Children database. These databases included all women who had delivered singleton between January 2007 and December 2008 in Korea. Out of the total 770,016 mothers, 30,959 (4.02%) were exposed to ritodrine during pregnancy, and 5583 (0.73%) of their children were identified as having autism, defined until 8 years of age. According to our analysis, the overall cumulative incidence of autism up to 8 years was 1.37% in ritodrine exposure group and 0.70% in ritodrine non-exposure group (p < 0.05, log-rank test). By Cox proportional hazard analysis, use of ritodrine in preterm birth was associated with significantly higher hazard of autism [adjusted hazard ratio: 1.23, 95% CI 1.04-1.47], after adjusting for confounding variables including maternal age, parity, cesarean section, preterm labor, steroid use, birth weight, gender, and preeclampsia. Thus, in utero exposure to ritodrine was associated with an increased risk of autism in their offspring.
Topics: Adult; Autistic Disorder; Child; Child, Preschool; Female; Humans; Incidence; Infant; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects; Republic of Korea; Ritodrine; Tocolytic Agents
PubMed: 33441922
DOI: 10.1038/s41598-020-80904-y