Maternal Adverse Events Associated with Antenatal Corticosteroids under Betamimetic Tocolysis in Preterm Birth Before 34 Weeks: An 11-Year Nationwide Database Study

Background Antenatal corticosteroids (ACS) are effective in improving the prognosis of preterm infants; however, their use rate in Japan is low, and large-scale studies on maternal safety are lacking. Therefore, this study aimed to clarify the association between ACS use and adverse maternal events in preterm births before 34 weeks of gestation treated with ritodrine hydrochloride (ritodrine). Methods Using nationwide data from fiscal year 2012 to 2022, we investigated 43,824 pregnant women who received ritodrine and experienced preterm births before 34 weeks of pregnancy. We calculated the trend in ACS implementation rates and examined their association with adverse maternal events using multivariate logistic regression analysis. Results The ACS implementation rates increased significantly from 26.9% to 59.8%, but the disparities between facilities widened. The ACS group had significantly higher rates of side effects of ritodrine listed in the package insert (listed adverse events; LAEs), heart failure, and pulmonary oedema. Multivariate analysis revealed that pulmonary oedema (adjusted odds ratio [aOR]: 2.45, 95% confidence interval [CI]: 1.82–3.30), heart failure (aOR: 1.55, 95% CI: 1.22–1.96), and LAEs (aOR: 1.17, 95% CI: 1.05–1.31) were associated with ACS use. However, when caesarean section was added as an adjustment variable, only the association with pulmonary oedema (aOR: 1.92, 95% CI: 1.25–2.95) remained significant. Conclusions Although the implementation rate of ACS is increasing, the differences between facilities are widening, making standardisation an urgent issue. Furthermore, because ACS use with ritodrine administration is strongly associated with pulmonary oedema independent of maternal severity, strict monitoring of vital signs, including respiratory rate, and appropriate information provision are essential. Trial Registration Not applicable.