Association between betamimetics tocolysis duration and maternal adverse events: a national real-world data analysis from Japan

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.