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

Abstract

To evaluate the risk of developing pulmonary edema in women exposed to nifedipine, magnesium sulfate (MgSO4), or both in a preterm setting. 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. 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. 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.