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

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.

Continuous variables are shown as median (interquartile range), and discrete variables are shown as n (%).
This analysis was performed using the "Basal data set". This analysis was performed using the "Hypoglycemia: Ritodrine-alone plus control set" derived from "Hypoglycemia set".
Final rate of injection (mg/min) just before cessation No usage -79

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Abbreviations: CI, confidence interval; h, hour(s); min, minute. This analysis was performed using the "Hyperkalemia: Both ritodrine and MgSO 4 plus control set" derived from "Hyperkalemia set".
Final rate of injection (mg/min) just before cessation No usage -79
This analysis was performed using "Hypoglycemia set".
a: Risk factors were determined based on both clinical relevance and univariable analysis as follows: combination of MgSO 4 and ritodrine, obstetrical complications, cesarean section, delivery at <35 wk, twins/triplets, infantile sex, SGA infants,largefor-gestational-age infants, Apgar score at 1 min <3, hypoglycemia at <48 h after birth, and hyperkalemia at <48 h after birth.
b: Multivariable analyses were performed using the same risk factors as in univariate analyses. However, birthweight was not used as a risk factor due to the close relationship with gestational weeks. In addition, the obstetric complication of TPL/shortened CL/CI was not used as a risk factor because either ritodrine or MgSO 4 was commonly used under these conditions. Excluding 989 patients with missing data for 16 variables, a total of 3,290 patients underweint multivariable analysis. Abbreviations: TPL, threatened preterm labor; CL, cervical length; CI, cervical incompetency.

Results
Participants 13* (a) Report numbers of individuals at each stage of study-eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed   *Give information separately for exposed and unexposed groups.