Preterm birth remains a major perinatal challenge, and management of women presenting with symptoms suggestive of early labor can shape admission, monitoring, medication use, and transfer pathways. In contemporary international practice, threatened preterm labor is generally managed within a risk-stratified framework, and tocolysis is used mainly for short-term obstetric purposes such as antenatal corticosteroid completion, maternal transfer, and fetal neuroprotection. In Japan, however, threatened preterm labor has often been diagnosed across a relatively broad clinical spectrum and managed with prolonged inpatient observation, bed rest, and extended ritodrine-based tocolysis. This review examines that pattern as a policy and practice problem rather than a narrow therapeutic controversy. It argues that the Japanese approach reflects a persistent evidence-practice gap involving broad diagnostic labeling, limited evidence supporting routine maintenance ritodrine, heterogeneous real-world practice, and guideline wording that remains more permissive than prohibitive. The available literature does not support prolonged maintenance ritodrine as routine care, while associations with maternal and neonatal safety concerns have been increasingly reported. Persistence is interpreted as potentially related to diagnostic breadth, institutional routines, limited therapeutic pathways, and uncertainty about de-escalation, not as evidence of a single cultural or medico-legal cause. This review proposes clearer negative recommendations on prolonged maintenance ritodrine, stronger diagnostic precision, and operational protocols that distinguish high-risk women requiring inpatient care from lower-risk women suitable for reassessment, treatment reduction, or outpatient follow-up.

[This corrects the article on p. 397 in vol. 33, PMID: 41488172.].

Pregnancy-associated myocardial infarction (PAMI) is a rare but potentially life-threatening condition for the mother and fetus. Pregnancy also confers a three- to fourfold increased risk of MI compared with the non-pregnant state. However, recognizing PAMI promptly in obstetric settings remains challenging. A 34-year-old Japanese primigravida at 30 weeks of gestation had been receiving ritodrine for preterm labor. On hospital day 2, approximately 4 h after discontinuation of tocolytics, repeat electrocardiography (ECG) indicated new ST-segment elevation in leads I, aVL, and V3-V6 without chest pain. High-sensitivity troponin I was 5392 pg/mL, CK-MB was 21 IU/L, and transthoracic ECG revealed mild apical hypokinesis. That night, prolonged fetal bradycardia prompted emergency Cesarean delivery. Maternal cardiac biomarkers then declined rapidly, and the ECG and wall-motion abnormalities resolved. Myocardial perfusion scintigraphy (day 5) and coronary computed tomography angiography (day 6) showed no perfusion defect or obstructive coronary disease. The infant, weighing 1546 g, was admitted to the neonatal intensive care unit. No adverse effects attributable to ritodrine were observed, and the infant was discharged on postnatal day 58. The report describes probable drug-induced PAMI temporally associated with β2-agonist tocolysis, with plausible mechanisms including transient coronary vasospasm and supply-demand mismatch in the hemodynamic milieu of pregnancy. This case suggests that women receiving β2-agonist tocolysis should be monitored for vital signs, electrolytes, and ECG changes. Even without chest pain, new ECG abnormalities or palpitations warrant immediate cardiac evaluation.

Peripartum pulmonary edema is rare but potentially life-threatening for both the mother and fetus. Unilateral pulmonary edema is particularly uncommon and can mimic pneumonia, delaying appropriate diagnosis because of atypical radiologic findings. A 28-year-old pregnant woman (G3P1) hospitalized for threatened preterm labor received ritodrine hydrochloride and magnesium sulfate. At gestational week 25, she suddenly developed chest pain, dyspnea, and hypoxemia. Chest X-ray revealed unilateral, left-sided pulmonary infiltrates. Cardiac evaluation showed no evidence of cardiogenic pulmonary edema, and infection was excluded, suggesting drug-induced pulmonary edema. Tocolytic agents were discontinued; however, respiratory failure necessitated emergency cesarean delivery. Postoperatively, pulmonary edema rapidly improved with intensive care. A detailed history revealed prolonged left lateral decubitus positioning before symptom onset. Drug-induced pulmonary edema combined with prolonged lateral positioning may predispose pregnant women to unilateral pulmonary edema. Awareness of positional effects during tocolytic therapy is important for early diagnosis.

The external cephalic version (ECV) is a manual procedure that rotates the fetus from breech to cephalic presentation through external abdominal manipulation. Major international guidelines recommend offering ECV at term to eligible women to reduce cesarean delivery rates. However, detailed technical guidance and standardized perioperative management remain limited. This review aims to provide a practical and clinically applicable guide based on an established institutional protocol, covering key preparatory measures, including patient selection and informed consent, a reproducible step-by-step technique, and post-procedure management. ECV is generally indicated for singleton breech pregnancies at or beyond 37 weeks of gestation, when vaginal birth is not contraindicated. Informed consent is required as an elective procedure, supported by balanced counseling on risks, benefits, and shared decision-making. Preprocedural management includes ultrasound assessment, fetal monitoring, and the use of ritodrine hydrochloride and neuraxial analgesia to enhance comfort and facilitate uterine relaxation. This technique emphasizes complete disengagement of the fetal buttocks, direction-specific wide-arc rotation of the fetal head while maintaining continuous upward lifting of the fetal buttocks, and secure engagement of the head beneath the pubic symphysis to prevent reversion. This step is followed by ultrasound confirmation that no umbilical cord or fetal extremity is present before the head. Safety was reinforced by performing the procedure in an operating room with immediate access for cesarean delivery and appropriate postprocedure monitoring. By offering a concise, reproducible approach and a supplementary procedural video, this review supports safer and more effective implementation of ECV and may help reduce unnecessary cesarean births.

Tocolytic therapy for preterm labour is recommended to be limited to 48 h to minimise maternal adverse events (MAEs), allowing antenatal corticosteroid administration and maternal transport to a tertiary facility. This retrospective cohort study clarified the association between ritodrine hydrochloride (ritodrine) infusion duration and MAEs in Japan. Data from 96,991 pregnant women who received ritodrine between April 2012 and March 2023 were analysed using the Diagnosis Procedure Combination database. Exposure was categorised as acute tocolysis (AT, ≤ 2 days) or maintenance tocolysis (MT, ≥ 4 days) to distinguish cases using day-based data. Overall, 21.45 and 78.55% patients received AT and MT, respectively. MT was strongly associated with venous thromboembolism (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.40–2.02), gestational diabetes mellitus (OR = 3.19, 95% CI = 2.50–4.06), and liver dysfunction (OR = 3.03, 95% CI = 2.02–4.55), whereas AT was more closely associated with heart failure and pulmonary oedema (OR = 1.30, 95% CI = 1.01–1.67; OR = 1.41, 95% CI = 1.01–1.96). MAE profiles varied by infusion duration. The stronger association with acute cardiovascular events in the AT group indicates that shorter treatment courses do not eliminate cardiovascular risk. Accordingly, maternal monitoring should be duration-specific, with intensive cardiopulmonary assessment from treatment initiation and heightened vigilance for metabolic and thrombotic complications during prolonged infusion.

Prolonged use of ritodrine hydrochloride (RT) for threatened preterm labor is discouraged in Western countries due to a lack of proven efficacy and severe maternal risks; however, it remains common in Japan. We report two rare cases of catheter-related bloodstream infections (CRBSI) in pregnant women undergoing long-term peripheral-line RT infusion. The first case involved Stenotrophomonas maltophilia bacteremia, a multidrug-resistant pathogen rarely reported in pregnancy. Despite limited antibiotic options, the patient recovered and delivered a healthy infant. The second case involved Achromobacter xylosoxidans bacteremia, treated successfully with ceftazidime, resulting in favorable maternal and neonatal outcomes. Both pathogens are opportunistic, typically affecting immunocompromised hosts or patients with indwelling devices, and their occurrence in otherwise healthy pregnant women underscores the risks of long tocolysis. These cases highlight CRBSI as a potentially life-threatening complication of long-term intravenous RT and emphasize the need to carefully balance its use against adverse outcomes.

Precise control over macromolecular chirality is critical for molecular recognition and targeted biological interventions. Herein, we report a pair of chiral gold nanozymes (l-/d-AuNEs) that mimic horseradish peroxidase (HRP)-like activity to catalyze the oxidative coupling of chiral phenolic monomers in a cellular environment. By introducing peptide ligands with both amino-acid-based configurational chirality and secondary structural chirality, the nanozymes enable high-yield enantioselective polymerization of the chiral Ritodrine (RITO), leading to the formation of enantiomeric dimers and high-molecular-weight polymers. The resulting polymers, Poly-l-RITO and Poly-d-RITO, exhibit significantly enhanced cytotoxicity relative to the monomer, with Poly-d-RITO showing a notably higher pro-apoptotic effect. Mechanistic studies reveal that Poly-d-RITO preferentially accumulates at the cell membrane and induces more severe membrane damage. These findings reveal a chirality-dependent biointerface effect and highlight the potential of nanozyme-driven asymmetric polymerization as an alternative strategy for chiral drug development and targeted cancer therapy.

The misuse of beta-agonist drugs as growth promoters in livestock production, highlighted by the cases of intoxication in Europe in the 1990s, has resulted in strict regulations in the European Union. These restrictions have required the development of increasingly sensitive analytical methods. In June 2022, the European Union Reference Laboratory (EURL BVL Berlin) released the Guidance Document on Minimum Method Performance Requirements (MMPRs), a technical guidance for analytical methods in residue control. The MMPRs represent the minimum concentrations that official laboratories should be able to reliably identify to analyze prohibited substances in different animal matrices. In this work, a qualitative screening method for 21 beta-agonists at half of MMPRs was developed and validated in animal lung and liver by UPLC-MS/MS technique according to Commission Implementing Regulation (EU) 2021/808 requirements. With regard to detection capability CCβ, the results obtained permitted the qualitative determination of 11 clenbuterol-like beta-agonists (Clenbuterol, Bromchlorbuterol, Brombuterol, Cimaterol, Cimbuterol, Clenpenterol, Clenproperol, Hydroxymethylclenbuterol, Mabuterol, Mapenterol, Tulobuterol) at 0.05 μg/kg and for 10 salbutamol-like beta-agonists (Carbuterol, Isoxsuprine, Clencyclohexerol, Ractopamine, Ritodrine, Salbutamol, Terbutaline, Zilpaterol, Fenoterol, Salmeterol) at 0.25 μg/kg. The method was validated for lungs and livers of different animal species (cattle, chicken, sheep, and swine): following the requirements of the above-mentioned Regulation. The method was found to be robust and specific.

Ritodrine hydrochloride, a beta-adrenergic tocolytic agent, can rarely cause acute noncardiogenic pulmonary edema, particularly in patients with multiple gestations or comorbidities. We report a case of a 28-year-old woman with twin pregnancy, type 1 diabetes, and hyperthyroidism that developed acute respiratory distress following ritodrine infusion. Imaging showed pulmonary edema, and point-of-care ultrasound (POCUS) revealed diffuse bilateral B-lines, preserved left ventricular function, and no signs of right heart strain or inferior vena cava plethora. These findings supported a diagnosis of noncardiogenic pulmonary edema. Emergency cesarean section was performed at 31[+6/7] weeks. Postoperatively, the patient's respiratory status improved, and both neonates had favorable outcomes. This case demonstrates the utility of POCUS as a rapid, radiation-free diagnostic tool for differentiating types of pulmonary edema in pregnant patients, enabling timely intervention and potentially improving maternal and neonatal outcomes. It also underscores the importance of vigilant monitoring when using beta-mimetic tocolytics in high-risk pregnancies.