Synergic interaction between ritodrine and magnesium sulfate on the occurrence of critical neonatal hyperkalemia: A Japanese nationwide retrospective cohort study

Abstract

Our aim was to evaluate the association between ritodrine and magnesium sulfate (MgSO₄) and the occurrence of neonatal hyperkalemia or hypoglycemia among late preterm infants in a retrospective cohort study. We used a nationwide obstetrical database from 2014. A total of 4,622 live preterm infants born at 32-36 gestational weeks participated. Fourteen risk factors based on both clinical relevance and univariate analysis were adjusted in multivariable logistic regression analyses. Neonatal hyperkalemia and hypoglycemia occurred in 7.6% (284/3,732) and 32.4% (1,458/4,501), respectively. Occurrence of hyperkalemia was associated with concomitant usage of ritodrine and MgSO₄ compared with no usage (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.09-2.15). Occurrence of hypoglycemia was associated with ritodrine alone (aOR 2.58 [CI 2.21-3.01]) and with concomitant usage of ritodrine and MgSO₄ (aOR 2.59 [CI 2.13-3.15]), compared with no usage, and was associated with long-term usage (≥ 48 hours) of ritodrine and cessation directly before delivery. In conclusion, in late preterm infants, usage of ritodrine together with MgSO₄ was associated with occurrence of critical neonatal hyperkalemia, and long-term usage of ritodrine and cessation directly before delivery were associated with neonatal hypoglycemia.

Figure 1

Patient Flowchart. “Basal data set” (N = 4,622) was created from 6,136 surveyed infants born at 32–36 gestational weeks. “Hypoglysemia set” (N = 4,501) was created from “Basal data set” after excluding 121 infants with unknown data on hypoglycemia; and “Hyperkalemia set” (N = 3,732) was created from “Basal data set” after excluding 890 infants with unknown data on hyperkalemia. “Hypoglycemia set” was divided into “Hypoglycemia: Ritodrine-alone plus control set” (Ritodrine-alone [N = 1,624] and control 1 without either ritodrine or MgSO₄ [N = 1,909]), “Hypoglycemia: MgSO₄-alone plus control set” (MgSO₄-alone [N = 233] and control 1), and “Hypoglycemia: Both ritodrine and MgSO₄ plus control set” (Both ritodrine and MgSO₄ [N = 735] and control 1). “Hyperkalemia set” was also divided into “Hyperkalemia: Ritodrine-alone plus control set” (Ritodrine-alone [N = 1,364] and control 2 without either ritodrine or MgSO₄ [N = 1,516]), “Hyperkalemia: MgSO₄-alone plus control set”, (MgSO₄-alone [N = 212] and control 2), and “Hyperkalemia: Both ritodrine and MgSO₄ plus control set” (Both ritodrine and MgSO₄ [N = 640] and control 2).