The maternal exposure of digoxin and flecainide in relation to the safety and effectiveness in the treatment of non-hydropic fetal tachycardia

BACKGROUND: Sustained fetal tachycardia requires transplacental anti-arrhythmic therapy. Little is known about the dose-concentration-effect correlation and safety in the mother, fetus, and newborn. OBJECTIVE: This study evaluates the relationship between maternal dose of digoxin and flecainide therapy for fetal tachycardia, maternal and umbilical cord concentrations, and side effects. METHODS: This was a retrospective case series. We included 28 pregnant women initially treated with digoxin monotherapy for fetal tachycardia between June 2007 and January 2023. The main end point was the correlation between maternal drug exposure, effect, and side effects. RESULTS: Oral digoxin monotherapy converted 9 fetuses (32%) to sinus rhythm after a median of 4.5 days (interquartile range [IQR] 3-6.5). Overall, 18 fetuses required additional oral flecainide (300 mg daily), resulting in a total conversion rate of 93% (26/28). Equal starting doses of digoxin caused similar maternal digoxin concentrations regardless of gestational age, with no significant difference between responders and non-responders (P = .504). Side effects, primarily nausea, led to dose reductions, but treatment remained effective. Maternal digoxin concentrations remained stable throughout pregnancy and little inter-patient variability was observed. Flecainide exposure varied both within and between patients. The median fetus/mother digoxin ratio was similar in both monotherapy (n = 3) and combination (n = 9) therapy groups (0.51 (IQR 0.28-0.76) vs 0.45 (IQR 0.39-0.64), P = .864). The median fetus/mother flecainide ratio was 0.82 (IQR 0.69-1.29). CONCLUSION: Digoxin monotherapy successfully treated fetal tachycardia in only 32% of cases. Adding flecainide improved response to 93%, although it increased side effects, which could be managed with dose reductions. Maternal digoxin levels were stable throughout pregnancy.