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

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.

Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan.

AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.

A singleton pregnancy with placental chorioangioma and hydrops fetalis complicated with mirror syndrome and ritodrine-induced side effects: a case report.

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.

Tocolytic treatment and maternal characteristics, obstetric outcomes, and offspring childhood outcomes among births at and after 37 weeks of gestation: the Japan environment and children's study.

PURPOSE: To evaluate differences in maternal characteristics and obstetric and offspring childhood outcomes between births at and after 37 weeks of gestation (referred to as term and post-term births) according to the use of tocolytic treatment. METHODS: Data for 63,409 women with singleton births at and after 37 weeks of gestation were analyzed using data from the Japan Environment and Children's Study (JECS). We compared maternal characteristics, obstetric outcomes, and offspring childhood outcomes between term and post-term births exposed and not exposed to tocolytic treatment. Additionally, multivariable logistic regression models were used to calculate adjusted odds ratios for offspring childhood outcomes with significant between-group differences in the univariable analysis, with term and post-term births without tocolytic agents as the reference group. RESULTS: We observed differences in maternal characteristics and obstetric outcomes between term and post-term births exposed and not exposed to tocolytic treatment. The incidence of offspring childhood developmental disorders showed no significant between-group differences. However, participants exposed to tocolytic agents had higher incidence of offspring childhood allergic disorders. The adjusted odds ratio for any of the offspring childhood allergic disorders in term and post-term births with tocolytic agents was 1.08 (95% confidence interval, 1.03-1.13). CONCLUSION: This study found no significant difference in the incidence of offspring developmental disorders between term and post-term births exposed and not exposed to tocolytic treatment. However, tocolytic treatment was associated with differences in maternal characteristics and obstetric outcomes, along with a marginal increase in the incidence of childhood allergic disorders in offspring.

Neonatal hyperkalemia associated with maternal ritodrine: A retrospective study.

BACKGROUND: We recently reported on a late preterm infant born at 36 weeks' gestation with serious arrhythmia due to hyperkalemia associated with long-term maternal ritodrine administration. It is unknown whether ritodrine alone increases the risk of neonatal hyperkalemia in infants born at 34-36 weeks' gestation. METHODS: This single-center, retrospective, cohort study enrolled late preterm infants (34-36 gestational weeks) born between 2004 and 2018. Cases with maternal magnesium sulfate use were not sufficient for statistical analysis and so were excluded from the study. Risk factors for the occurrence of hyperkalemia were determined based on clinical relevance and previous reports. RESULTS: In all, 212 late preterm infants with maternal ritodrine use and 400 infants without tocolysis were included in the study. Neonatal hyperkalemia occurred in 5.7% (12/212) in the ritodrine group and 1.8% (7/400) in the control group. The risk of neonatal hyperkalemia was significantly increased by maternal ritodrine administration with a crude odds ratio (OR) of 3.37 (95% confidence interval [CI]: 1.30-8.69; p < 0.01) and an adjusted OR of 3.71 (95% CI: 1.41-9.74; p < 0.01) on multivariable analysis. Long-term tocolysis (≥28 days) with ritodrine increased the risk of neonatal hyperkalemia with 9.3% (11/118) of infants developing hyperkalemia (adjusted OR 4.86; 95% CI: 1.59-14.83; p < 0.01). Neonatal hyperkalemia was not found within 2 weeks of ritodrine administration. CONCLUSION: This research suggests that late preterm infants born after long-term ritodrine administration are at risk of neonatal hyperkalemia and require special attention.

Long-term vs short-term tocolysis with ritodrine hydrochloride: Propensity score-matched analysis.

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.

Ritodrine-induced rhabdomyolysis and psychiatric symptoms: a case report and literature review.

BACKGROUND: Ritodrine hydrochloride, a ß2-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 235/7 GW and 400 µg/min at 271/7 GW. Magnesium sulfate was added to the ritodrine regimen at 215/7 GW in dosage of 1-2 g/h. Psychiatric symptoms appeared at 245/7, 265/7, and 273/7 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.

Effect of ritodrine hydrochloride infusion on fetal movement with the use of a fetal movement acceleration measurement recorder (FMAM recorder).

AIM: To investigate the effect of ritodrine hydrochloride infusion on fetal movement. METHOD: We gathered 20 pregnant women who received ritodrine hydrochloride infusion as the treated group, and 147 pregnant women who did not as the control group. All women recorded gross fetal movement with the fetal movement acceleration measurement recorder after 28 gestational weeks. The record was divided into epochs of 10 s, and the ratio of movement-positive epochs to all epochs was calculated as the fetal movement index. Furthermore, the mean duration and the mean number per hour of no-fetal movement period, where the fetus did not move for 5 min or more, were calculated as the indexes of no-fetal movement. All indexes were compared between the two groups at 28-31 and 32-35 gestational weeks. RESULTS: The fetal movement indexes (%) were 17.29 ± 7.46 (mean ± SD) in the control group and 13.65 ± 7.13 in the treated group at 28-31 weeks (p = 0.139). At 32-35 weeks, they were 14.55 ± 6.43 and 18.50 ± 5.33, respectively (p = 0.03). Similarly, the no-fetal movement indexes (min, times/h) were 15.03 ± 10.99 and 1.61 ± 0.88, and 18.70 ± 15.80 and 1.75 ± 0.96 (p = 0.824, and 0.673) at 28-31 weeks. At 32-35 weeks, they were 18.13 ± 10.88 and 1.95 ± 0.97, and 9.20 ± 5.51 and 1.14 ± 0.71, respectively (p = 0.003, and 0.003). CONCLUSION: Ritodrine hydrochloride infusion increased the fetal movement and decreased the no-fetal movement period at 32-35 weeks.

Efficacy of atosiban combined with ritodrine on spontaneous threatened preterm birth and its effect on PAF and fFN levels.

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.

Antenatal mgnesium sulfate and ritodrine increased potassium levels in preterm infants: A cohort study.

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.

Efficacy of atosiban combined with ritodrine in the treatment of threatened preterm labor and related risk factors of different pregnancy outcomes.

OBJECTIVE: To investigate the efficacy of atosiban combined with ritodrine in threatened preterm labor (TPL) treatment and analysis of related risk factors of different pregnancy outcomes. METHODS: A retrospective study was conducted on the clinical data of 127 patients with TPL who were hospitalized in the Children's Hospital of Shanxi and Women's Health Center of Shanxi from January 2020 to November 2021. There from, 58 patients treated with ritodrine were seen as the control group (CG), and 69 treated with atosiban and ritodrine were regarded as the joint group (JG). The inhibition rate after treatment was compared, and the changes of tissue inhibitor of metalloproteinase-1 (TIMP-1), nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in the amniotic fluid before and after treatment were assessed. The pregnancy outcomes of patients were recorded, and the risk factors of adverse pregnancy outcomes were analyzed. The full-term delivery rate, cesarean section rate and neonatal Apgar score >7 were compared, and their adverse reactions were evaluated. RESULTS: Compared with the JG, the improvement of uterine contraction in the CG was obviously lower, and so was the inhibition rate (P<0.05). The rates of full-term delivery and neonatal Apgar score >7 in the CG were lower than those in the JG, while that of cesarean section was higher (P<0.01). After treatment, the TIMP-1 level in the amniotic fluid in the CG was markedly lower (P<0.001), while the NO, IL-6 and PGE2 levels were higher (P<0.001) as compared with the joint group. The total incidence of adverse reactions in the JG was lower than that in the CG (P<0.05). Logistics regression analysis revealed that age<26 and use of Atosiban combined with Ritodrine are protective factors for pregnancy outcomes, while BMI≥20 before pregnancy is a risk factor for adverse pregnancy. CONCLUSION: Atosiban combined with ritodrine can improve the condition of TPL patients, enhance the treatment efficacy, and reduce the occurrence of adverse pregnancy outcomes.

The protective effects of ritodrine against hypoxia/reoxygenation-induced injury in endometrial stromal cells.

Endometriosis (EMS) is often observed in women of childbearing age and significantly impacts patients' quality of life. Ritodrine is a ß2 receptor agonist applied for relaxing the uterine smooth muscle. Its inhibitory effects on inflammation have recently been noted. The present study explored the protective impact of Ritodrine on hypoxia/reoxygenation (H/R)- induced injury in endometrial stromal cells (ESCs). Human ESCs (HESCs) were treated with Ritodrine (0.1, 0.5 µM) for 24 h, followed by exposure to H/R for 6 h. Ritodrine ameliorated H/R-induced higher reactive oxygen species (ROS), declined glutathione (GSH) concentration and increased production of tumor necrosis factor-α (TNF-α), interleukin- 6 (IL-6), and monocyte chemotactic protein 1 (MCP-1) in HESCs. Furthermore, Ritodrine ameliorated the H/R-induced higher nuclear level of nuclear factor κ-B (NF-κB) p65 expression and increased luciferase activity of the NF-κB promoter. In addition, we show that Ritodrine mitigated H/R-induced higher estrogen receptor α (ER-α) expression in HESCs. Interestingly, overexpressing ER-α abolished the regulatory effects of Ritodrine on oxidative stress and the NF-κB pathway-mediated inflammation. Collectively, our data reveal that Ritodrine alleviated H/R-induced injury in ESCs by inhibiting the ER-α/NF-κB pathway.

Betamethasone use and risk factors for pulmonary edema during the perinatal period: a single-center retrospective cohort study in Japan.

BACKGROUND: A few studies have reported that maternal administration of antenatal corticosteroids increased the risk of pulmonary edema (PE). However, despite the increasing usage rate of betamethasone as antenatal corticosteroid, maternal administration of betamethasone as a risk factor for PE has not been well studied. This study aimed to evaluate how maternal backgrounds and complications, tocolytic agents, and betamethasone affect the incidence of PE during the perinatal period and determine the risk factor for PE. METHODS: This was a single-center retrospective cohort study in Kurashiki, Japan. The study subjects were patients who had been admitted to our hospital for perinatal management including pregnancy, delivery and puerperium between 2017 and 2020. The primary outcome measure was defined as the incidence of PE during hospitalization. First, in all study subjects, Cox proportional hazards model was used to determine the risk factor for PE during the perinatal period. Next, using propensity score matching, we divided the patients into the betamethasone and betamethasone-free groups and examined the association between betamethasone use and the incidence of PE with Cox proportional hazards model. RESULTS: During the study period, 4919 cases were hospitalized, and there were 16 PE cases (0.3%). In all analyzed subjects, the occurrence of PE was significantly associated with preeclampsia (hazard ratio 16.8, 95% confidence intervals (CI) 5.39-52.7, P < 0.001) and the combined use of the tocolytic agents such as ritodrine hydrochloride and magnesium sulfate, and betamethasone (hazard ratio 11.3, 95% CI 2.66-48.1, P = 0.001). In contrast, after propensity score matching, no statistically significant difference was found between the betamethasone and betamethasone-free groups in the incidence of PE (hazard ratio 3.19, 95% CI 0.67-15.3, P = 0.145). CONCLUSIONS: A combined use of tocolytic agents and antenatal corticosteroids such as betamethasone may be an independent risk factor for PE during the perinatal period. On the other hand, betamethasone use alone may not be associated with the incidence of PE. When tocolytic agents and betamethasone are administrated to pregnant women, it is important to pay attention to the appearance of maternal respiratory symptoms.

Ritodrine in external cephalic version: is it effective and safe?

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.

High-throughput Screening in Combination With a Cohort Study for Iodothyronine Deiodinases.

Regulatory mechanisms of iodothyronine deiodinases (DIOs) require further elucidation, and conventional methods for evaluating DIOs are unsuitable for high-throughput screening (HTS). Here we explored factors of transcriptional regulation of 3 types of DIOs (DIO1, DIO2, and DIO3) from a chemical library using our designed HTS. We constructed HTS based on a promoter assay and performed a screen of 2480 bioactive compounds. For compounds that were clinically approved, we validated hit compounds through a retrospective cohort study in our department that evaluated changes in thyroid function in patients using the compounds as drug therapy. Furthermore, we verified the involvement of DIOs using mice treated with the compounds. Of the hit compounds, 6 and 7 compounds transcriptionally up- and downregulated DIO1, respectively; 34 transcriptionally upregulated DIO2; and 5 and 2 compounds transcriptionally up- and downregulated DIO3, respectively. The cohort study clarified the clinical effects of some hit compounds: ritodrine increased free triiodothyronine (fT3)/free thyroxine (fT4) ratio and decreased serum thyroid-stimulating hormone (TSH) levels, tadalafil increased serum fT3 levels, and tyrosine kinase inhibitors (TKIs) decreased serum fT3 and fT4 levels and increased serum TSH levels. Following in vivo experiments using treated mice, consistent results were observed in ritodrine, which upregulated DIO2 in the thyroid gland. In conclusion, we completed HTS for DIOs and obtained attractive hit compounds. Our cohort study revealed the clinical significance of ritodrine, sildenafil, and TKIs. We hope our unique method will contribute to analyzing various targets and lists of hit compounds will promote understanding of DIOs.

Associations of GNAS and RGS Gene Polymorphisms with the Risk of Ritodrine-Induced Adverse Events in Korean Women with Preterm Labor: A Cohort Study.

Ritodrine, a ß2-adrenergic receptor agonist, is among most commonly prescribed tocolytic agents. This study aimed to evaluate the associations of single nucleotide polymorphisms in GNAS, RGS2, and RGS5 with the risk of ritodrine-induced adverse events (AEs) and develop a risk scoring system to identify high-risk patients. This is the prospective cohort study conducted at the Ewha Woman's University Mokdong Hospital between January 2010 and October 2016. Pregnant women were included if they were treated with ritodrine for preterm labor with regular uterine contractions (at least 3 every 10 min) and cervical dilation. A total of 6, 3, and 5 single nucleotide polymorphisms (SNPs) of GNAS, RGS2, and RGS5 genes were genotyped and compared in patients with and without ritodrine-induced AEs. A total of 163 patients were included in this study. After adjusting confounders, GNAS rs3730168 (per-allele odds ratio (OR): 2.1; 95% confidence interval (95% CI): 1.0-4.3) and RGS2 rs1152746 (per-allele OR: 2.6, 95% CI: 1.1-6.5) were significantly associated with ritodrine-induced AEs. According to the constructed risk scoring models, patients with 0, 1, 2, 3, 4, and 5 points showed 0%, 13%, 19%, 31%, 46%, and 100% risks of AEs. This study suggested that GNAS and RGS2 polymorphisms could affect the risk of AEs in patients treated with ritodrine.

Acute tocolysis for intrapartum nonreassuring fetal status: how often does it prevent cesarean delivery? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the effectiveness of intrapartum acute tocolysis for nonreassuring fetal heart rate tracing in decreasing the incidence of cesarean delivery. Secondary outcomes included modes of delivery other than cesarean delivery, successful acute tocolysis, time-to-delivery interval, and short-term perinatal outcomes. DATA SOURCES: Searches were performed in MEDLINE/PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and Reviews, ClinicalTrials.gov, and the International Clinical Trials Registry Platform from the inception of each database until February 2022. STUDY ELIGIBILITY CRITERIA: Selection criteria included randomized controlled trials of laboring patients with singleton gestations randomized to receive intrapartum acute tocolysis for nonreassuring fetal heart rate tracing, as defined by the original trial. METHODS: All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. A frequentist network-meta-analysis was performed. RESULTS: Four randomized clinical trials were eligible, including 605 patients with nonreassuring fetal heart rate tracing and singleton gestations at gestational ages >32 weeks. The cesarean delivery rate was similar among patients managed with different types of acute tocolysis. Acute tocolysis, compared with emergency delivery, was associated with improved neonatal acid-base status (notably decreasing the prevalence of base deficit >12 mmol/L [beta-2 agonists odds ratio, 0.61; 95% confidence interval, 0.37-0.99] and the rate of neonatal intensive care unit admission [beta-2 agonists odds ratio, 0.42; 95% confidence interval, 0.22-0.78]) and with an increase in the time-to-delivery interval (beta-2 agonists mean difference, 17.62 minutes; 95% confidence interval, 15.66-19.58); there was no reduction of cesarean delivery rate, showing an increased rate with atosiban and beta-2 agonists. CONCLUSION: The cesarean delivery rate was not reduced by acute tocolysis when used for nonreassuring fetal heart rate tracing during labor. Acute tocolysis is associated with improved short-term fetal outcomes and safely increases the time-to-delivery interval.

Acute Primary Angle Closure Caused by Plateau Iris After Ritodrine Use in a Primigravid Woman Successfully Treated With Clear-Lens Extraction: A Case Report.

Acute primary angle closure (APAC) is rare in young adults (those under approximately 40 years old) and pregnant women. Here, we report the case of a 37-year-old primigravid woman with APAC caused by plateau iris after the use of ritodrine (a ß2 stimulator) that was successfully resolved by clear-lens extraction five months after delivery. The patient presented with pain in her right eye after ritodrine infusion for threatened premature labor at 23 weeks of gestation. Her visual acuity was 20/40, and her intraocular pressure (IOP) was 31 mmHg in her right eye. The patient was diagnosed as having APAC with plateau iris based on ultrasound biomicroscopy (UBM) findings of irido-angle touch, anterior dislocation of the ciliary process, and an absent ciliary sulcus. The effectiveness of treatment with pilocarpine eyedrops was limited, and argon laser peripheral iridoplasty did not succeed in reducing IOP. An immediate resolution was achieved with clear-lens extraction. IOP has since stayed within 14-16 mmHg without any medication for seven years. This is the first reported case of APAC complicated with plateau iris after ritodrine use in a pregnant woman. This condition is rare in young adults, making it difficult to diagnose; however, UBM can be of great help. In this case, clear-lens extraction led to a successful outcome. Our case suggests that attention should be paid to drug associations when APAC occurs with plateau iris.

Four kinds of tocolytic therapy for preterm delivery: Systematic review and network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Premature birth affects more than 15 million infants, as well as mothers and families around the world. With the relaxation of the two-child policy, the problem of premature birth has become relatively prominent in China. According to statistics, China had a birth population of 15.23 million in 2018, with a considerably large number of premature births. This study aims to evaluate the efficacy and safety of tocolysis in the treatment of preterm delivery, provide clinical evidence for medical staff and promote the self-management of patients with premature births. METHODS: Four English databases (PubMed, Embase, Cochrane Library and Web of Science) were retrieved by computer, the retrieval time was from the establishment of each database to November 2021, and the randomized controlled trials for the treatment of preterm delivery were screened according to the pre-set natriuretic exclusion criteria. After literature screening, data selection and risk of bias evaluation were independently conducted by two researchers. R 4.1.1 and Stata 17.0 software were used for statistical analysis. RESULTS AND DISCUSSION: A total of 44 RCTs were included, including 6939 patients. The results of network meta-analysis reveal that in terms of effectiveness, indomethacin was the most effective intervention measure, followed by nifedipine, and the difference was statistically significant; regarding safety, nifedipine was the safest intervention measure, followed by indomethacin, and the difference was statistically significant; and in respect of adverse reactions, ritodrine had the highest probability, and the difference was statistically significant. WHAT IS NEW AND CONCLUSION: Nifedipine may be better for delayed delivery and less likely to produce adverse pregnancy outcomes, followed by indomethacin. Limited by the number and quality of recipient studies, the aforementioned conclusions need to be verified through more high-quality studies. At the same time, the focus should be on patients with twin pregnancy and patients with clinical manifestations of extreme preterm delivery.

Toxic epidermal necrolysis induced by ritodrine in pregnancy: A case report.

BACKGROUND: Preterm birth accounts for about 12% of all pregnancies worldwide and is the leading cause of neonatal morbidity and mortality. In order to avoid premature birth and prolong gestational age, tocolytics are the first and the best choice. Ritodrine is the most commonly used tocolytic medication. However, side effects such as pulmonary edema, hypokalemia, and hyperglycemia are known. Here we report a rare but serious side effect-toxic epidermal necrolysis (TEN)-caused by ritodrine. CASE SUMMARY: A woman (31 years, gravida 4, para 2) was hospitalized because of premature contractions at 27 + 6 wk of gestation. A skin rash with pruritus appeared at 32 + 3 wk of gestation after administration of ritodrine, indomethacin, and dexamethasone, and it spread throughout the whole body in 3 d, particularly the four limbs. After 11 d' treatment, she was diagnosed with TEN. An emergency cesarean section was performed immediately to deliver the baby and intensive symptomatic treatment was promptly commenced after delivery. She recovered from the severe condition without any sequelae except for slight pigmentation after symptomatic treatment. CONCLUSION: When a skin rash appears during the administration of ritodrine, we are supposed to consider the risk of TEN.