Preterm birth (PTB) remains a leading cause of infant mortality and morbidity, significantly affecting the long-term health, welfare, and development of newborns. Tocolytics, such as ritodrine, a β₂-adrenergic receptor agonist, are widely used in developing countries due to their affordability for preventing PTB by inhibiting uterine contractions. However, ritodrine's short half-life necessitates frequent administration, and prolonged high-dose usage often leads to serious maternal side effects, prompting discontinuation. The uterine first-pass effect, where vaginally administered drugs preferentially target the uterus, can enhance drug concentration in uterine tissue while minimizing systemic absorption and side effects. This study designed a kind of ritodrine-loaded thermosensitive gel (Gel@Rit) to intervene in PTB by exploiting the uterine first-pass effect and investigate its underlying mechanisms. The gel, formulated with poloxamer, demonstrated excellent temperature sensitivity and viscosity, ensuring sustained ritodrine release in vitro. Plasma pharmacokinetic and tissue distribution studies in pregnant mice confirmed the uterine first-pass effect, showing significantly higher drug concentrations in the uterus and markedly lower plasma levels following Gel@Rit administration. The distinctive drug-time curve in Gel@Rit-treated mice, along with uterine tissue fluorescence profiles, elucidated four mechanisms of uterine localization: diffusion through reproductive tract cavities, penetration via vaginal and uterine structures, diffusion through systemic circulation, and retrograde transvaginal veno-uterine artery exchange. This study provides valuable insights into vaginal drug delivery research methodologies, advancing therapeutic strategies for uterine-related conditions and benefiting clinical outcomes in PTB prevention.

2024-12-01·International Journal of Gynecology & Obstetrics

External cephalic version following prior cesarean delivery: A comparative cohort analysis

Article

作者: Guijarro‐Campillo, Alberto Rafael ; Araico‐Rodríguez, Fernando ; de Paco, Katy ; Blanco‐Carnero, José Eliseo ; Gallego‐Pozuelo, Rosa María ; Nieto‐Díaz, Aníbal ; Sánchez‐Romero, Javier ; Herrera‐Giménez, Javier ; Dahmouni‐Dahmouni, Hajar

AbstractObjectiveTo analyze the success rate of external cephalic version (ECV) in pregnant women with a history of previous cesarean section, as well as to describe the rate of complications associated with the procedure.MethodsA retrospective cohort study of women who were offered an ECV at “Virgen de la Arrixaca” Clinic University Hospital (Murcia, Spain) between January 2014 and December 2023. We collected data for previous cesarean delivery, obstetric history, fetal presentation, amniotic fluid volume, ECV success rate, complications related to ECV, mode of delivery, and neonatal outcomes. The study confidently performed ECV under sedation with propofol and tocolysis with ritodrine. Univariate and multivariate analyses were conducted to compare the success rate of ECV, ECV complications, and mode of delivery between women with and without previous cesarean sections.ResultsOf 1116 pregnant women who were offered ECV, 911 were included in the study, with 42 having a previous cesarean section. The success rate of ECV in pregnant women with a previous cesarean section was 78.6% (adjusted odds ratio 1.18; 95% confidence interval 0.49–2.86; P = 0.708), with a low complication rate of 9.5%, such as non‐reassuring fetal heart rate (7.1%) or major vaginal bleeding (2.4%). Of the women who attempted a vaginal delivery after ECV, 80.8% were successful.ConclusionsThese findings support that ECV is a safe and effective option for women with a previous cesarean section, with success rates comparable to those in women without a previous cesarean section.

2024-10-01·International Journal of Gynecology & Obstetrics

Risks of maternal cardiopulmonary events associated with ritodrine for tocolysis: A national database linkage study in 1 831 564 pregnant women

Article

作者: Chen, Wen‐Wen ; Liang, Hsun‐Yin ; Huang, Wei‐I ; Lin, Chih‐Wan ; Chao, Pi‐Hui ; Hsiao, Fei‐Yuan ; Chan, K. Arnold ; Chen, Yi‐Yung

AbstractObjectiveReal‐world data on cardiopulmonary events among pregnant women receiving β‐agonist therapy are scarce. In the present study, we aimed to examine the absolute and relative risks of maternal cardiopulmonary events associated with the use of β‐agonist ritodrine during pregnancy.MethodsBy linking Taiwan's National Birth Certificate Application Database with National Health Insurance data, 1 831 564 pregnancies at ≥20 weeks' gestation were identified. Age‐standardized incidence rates of cardiopulmonary events among pregnant women exposed to ritodrine were estimated. Nested case–control analyses were conducted to evaluate the relative risk of pulmonary edema, heart failure, and arrhythmia associated with prior ritodrine use. Cases and controls were matched using risk set sampling, and adjusted odds ratios were estimated using conditional logistic regression models.ResultsA total of 189 cases of pulmonary edema, 126 cases of heart failure, and 162 cases of arrhythmia were identified (corresponding age‐standardized incidence rates: 20.90, 8.35, and 16.63 per 100 000 among pregnant women only exposed to oral ritodrine; 91.28, 36.01, and 14.61 per 100 000 among those ever exposed to intravenous ritodrine). Exposure to oral ritodrine was associated with a lower increased risk of pulmonary edema (aOR 1.76; 95% CI: 1.12–2.76) and arrhythmia (2.21; 1.47–3.32) whereas exposure to ritodrine injection was associated with a significantly higher risk of pulmonary edema (10.56; 6.39–17.45), arrhythmia (4.15; 1.99–8.64), and heart failure (5.58; 2.27–13.74).ConclusionsPregnant women receiving intravenous ritodrine therapy had higher cardiopulmonary risks and should be intensively monitored. While the relative risk associated with oral ritodrine is not pronounced, it should be used judiciously among pregnant women as well.

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