303 - Neonatal rebound hyperkalemia associated with maternal ritodrine: a retrospective study.

Long-term tocolysis with ritodrine is commonly used in Japan. We recently reported on a late preterm infant born at 36 gestational weeks with serious arrhythmia due to hyperkalemia associated with long term maternal ritodrine administration.  It is unknown whether ritodrine alone increases the risk of neonatal hyperkalemia in late preterm infants born at 34-36 gestational weeks.

 

Objective: To elucidate the association between risk of neonatal hyperkalemia and maternal ritodrine use in late preterm infants.

Design/Methods:

This single center retrospective cohort study enrolled late preterm infants born at 34-36 gestational weeks between 2004 and 2018. Cases with maternal MgSO₄ use were not sufficient for statistical analysis, and so they were excluded. Peak K⁺ concentrations during the first 72 h were recorded, and neonatal hyperkalemia was defined as K⁺ > 6.0 mEq/L. Risk factors for the occurrence of hyperkalemia were determined on the basis of clinical relevance and previous reports. Multivariable regression analyses were performed to adjust the confounding variables that were statistically significant in univariate analysis. 

 


Results:

In all, 212 late preterm infants with maternal ritodrine and 400 infants without tocolysis were included in the study (Fig.1). Nineteen (3.1%) were diagnosed with neonatal hyperkalemia. The median peak K⁺ time was 14 h after birth. No one received infusion with potassium. The incidence of ritodrine use was significantly higher in the neonatal hyperkalemia group than in the non-hyperkalemia group (63.2% vs. 33.7%, P< 0.05, Table 1). The risk of neonatal hyperkalemia was significantly increased by maternal ritodrine administration, with a crude odds ratio (OR) of 3.37 (95% confidence interval [CI] 1.30-8.69; p < 0.01) and an adjusted OR of 4.86 (95% CI 1.59-14.83; p < 0.01) on multivariable analysis (Table 2). Long-term tocolysis (≥28 days) with ritodrine increased the risk of neonatal hyperkalemia, with 9.3% (11/118) of infants developing hyperkalemia (adjusted OR 10.40; 95% CI 3.20–33.88; p < 0.001). Neonatal hyperkalemia was not found within 2 weeks of administration.


Conclusion(s): This research suggests that late preterm infants born after long-term ritodrine administration , who are often cared at maternal ward, are at risk of neonatal hyperkalemia and require special attention. We hypothesize  that ritodrine crosses the placenta and stimulates fetal pancreatic beta cells to promote insulin secretion, but when ritodrine is interrupted at birth, insulin secretion is reduced and potassium begins to leak from the cells.
Figure PAS ver 2.001.jpeg

Figure PAS ver 2.002.jpeg

Figure 1 .jpeg