43 Correlation between maternal, fetal and neonatal digoxin and flecainide concentrations and (side) effects in mother and child, treated for fetal supraventricular tachycardia – a case series to improve dosing

Introduction Sustained fetal tachycardia often requires transplacental antiarrhythmic therapy. Little is known about the dose-concentration-effect correlation in the mother, fetus, and newborn. Our aim was to evaluate the relationship between perinatal digoxin and flecainide therapy, measured maternal and umbilical concentrations, and effect. Methodology We conducted a retrospective case series including all pregnant women with their fetuses treated for fetal tachycardia in the period from January 2017 until February 2023. The main study endpoints were effects, expressed as fetal conversion to sinus rhythm, maternal side effects, and digoxin and flecainide serum concentrations in relation to the applied doses at the time of conversion. Results Twenty-one fetuses were included at a median gestational age of 30 (IQR 29–32) weeks with a median fetal heart rate of 240 (IQR 231–266) bpm. Digoxin monotherapy (1.5 mg followed by 0.75 mg daily) (n=9) converted 4 (44%) fetuses to sinus rhythm after a median time of 2.0 (IQR 1.8–2.0) days with digoxin through concentrations of 1.4 (IQR 1.4–1.5) µg/L. Five fetuses did not convert with dioxin monotherapy, despite of median through concentrations of 1.15 (IQR 0.95–1.43) µg/L. One of these fetuses switched to sotalol, without effect. In the other 4 fetuses flecainide was added after 4 days to reach conversion. Flecainide monotherapy (300 mg daily) (n=3) converted 3 (100%) fetuses to sinus rhythm after a median time of 1.0 (IQR 1.0–2.0) day with a median through concentration of 0.97 (IQR 0.33–0.66) mg/L. Combination therapy of flecainide and digoxin converted 4 of the 8 (50%) hydropic fetuses after 2.0 (IQR 1.8–2.5) days with through concentrations digoxin of 1.4 (IQR 1.1–1.6) µg/L and flecainide 0.40 (IQR 0.32–0.46) mg/L. Conversion was not reached in 4 fetuses despite of median through concentrations of digoxin 1.2 (IQR 1.0–1.4) µg/L and flecainide 0.47 (IQR 0.34–0.58) mg/L. Two of these fetuses eventually converted by adding a beta blocker. Cardiac complications and mild side effects occurred in 90% of the mothers. Fetal to maternal umbilical cord ratios were available for two cases, 0.57 and 0.63 for digoxin and 0.85 and 1.23 for flecainide. Conclusion Transplacental antiarrhythmic resulted in successful conversion in 16(76%) of the fetuses and mild maternal side effects. Maternal plasma concentrations and umbilical cord ratios were high which may indicate that lower doses may also be effective.