Effect of magnesium sulfate and nifedipine on the risk of developing pulmonary edema in preterm births

Objective: To evaluate the risk of developing pulmonary edema in women exposed to nifedipine, magnesium sulfate (MgSO4), or both in a preterm setting. Study design: We carried out a retrospective case-control study at a large tertiary care center from 2007 to 2012. Cases of pulmonary edema were age, and gestational age matched to controls at a ratio of 1 case to 4 controls. Logistic regression analysis was used to estimate the effect of nifedipine and/or MgSO4 on the development of pulmonary edema while controlling for predetermined confounding variables. Stepwise logistic regression analysis was used to evaluate additional risk factors of pulmonary edema. Results: A total of 150 charts were reviewed (28 cases and 122 controls). Nifedipine did not increase the odds of developing pulmonary edema [adjusted odds ratio (OR)=1.22 (confidence interval (CI) 0.50, 3.01), P=0.67], whereas exposure to MgSO4, or both MgSO4 and nifedipine, significantly increased the risk of developing pulmonary edema [adjusted OR=3.91 (CI 1.44, 10.65), P=0.008 and adjusted OR=4.75 (CI 1.15, 19.71), P=0.032, respectively]. In the stratified analysis, this association persisted even in nonpreeclamptic women [nifedipine: adjusted OR=0.91 (CI 0.33, 2.52), P=0.852; MgSO4: adjusted OR=3.51 (CI 1.26, 9.76), P=0.016; both: adjusted OR=3.39 (0.76, 15.07), P=0.108]. Other independent risk factors for pulmonary edema were multi-fetal pregnancy, azithromycin, and erythromycin administration. Conclusion: MgSO4 treatment is strongly associated with the development of pulmonary edema when used either as a tocolytic agent or for seizure prophylaxis. In light of the availability of safer alternatives, MgSO4 should be used for tocolysis only in cases whereby the benefits clearly outweigh the risks.